1. science
2. medicine
3. surgery

2014
MSTS
ANNUAL MEETING
Houston, Texas October 9 – 11, 2014
ABSTRACTS
Valerae O. Lewis, MD, Program Chair
Kristy L. Weber, MD, President
2014 MSTS Annual Meeting
October 9-11, 2014
Omni Houston Hotel
Houston, TX
Valerae Lewis, MD, Program Chair
Kristy Weber, MD, President
Educational Goals and Objectives
At the conclusion of this CME activity, the attendee should be able to:
Recognize the new options for limb salvage surgery for patients with malignant bone and soft tissue tumors;
Identify and better manage complications that occur after limb salvage surgery;
Report recent progress in basic and translational research as it relates to the diagnosis and/or prognosis of the orthopaedic
oncologic patient;
Identify new approaches for targeted therapy to treat patients with primary or metastatic bone or soft tissue tumors;
Discuss new surgical and adjuvant treatments for benign bone and soft tissue tumors;
Formulate a differential diagnosis for bone and soft tissue tumors and tumor-like conditions based upon clinical, radiologic,
and pathologic information.
Thursday, October 9, 2014
2:00 - 5:00 PM
2:00 - 6:00 PM
2:00 - 5:00 PM
2:00 - 5:00 PM
6:00 - 7:30 PM
Executive Committee Meeting
Registration
Poster Exhibit Set-up
Technical Exhibit Set-up
Welcome Reception
Friday, October 10, 2014
7:00 - 8:00 AM
7:00 AM - 5:30 PM
7:00 AM - 5:30 PM
7:30 AM
7:35 AM
7:40 AM
7:45 AM
Breakfast
Registration
Poster/Technical Exhibits
Welcome
Tribute to Dr. William Enneking
Introduction of Founder's Lecture
Founder's Lecture: Leaders, Mentors and Path for
Continuity
Valerae Lewis, MD
Mark Scarborough, MD
Kristy Weber, MD
Luis Muscolo, MD
Session I: Prostheses and Allografts
Moderators: Cindy Kelly, MD, Richard McGough, MD
Long Term Outcomes Of Endoprosthetic
Reconstruction For Periarticular Tumors Of Matthew Houdek, MD
Mayo Clinic, Rochester, MN
The Knee
Retrospective Evaluation Of The Incidence
Of Early Periprosthetic Infection With SilverTreated Endoprostheses In High-Risk
Krishna Reddy, MBBS, MS, FRCS
Patients: Case Control Study
Royal Orthopaedic Hospital, Birmingham, UK
Luis Aponte-Tinao, MD
Infections In Massive Bone Allografts.
Italian Hospital of Buenos Aires, Buenos Aires,
Management And Results.
Argentina
Late Complications And Long-Term
Outcomes Following Revision Of A Total
Hip Arthroplasty Performed For Oncological Benjamin Wilke, MD
Mayo Clinic, Rochester, MN
Resection
Tranexamic Acid Does Not Increase
Herrick Siegel, MD
Incidence Of Dvt Or Pte In Sarcoma
University of Alabama at Birmingham
Surgery
An Osseointegrated Percutaneous
Prosthetic System For Treatment Of
Transfemoral Amputees: Results From The Orjan Berlin, MD
Department of Orthopaedics, Sahlgrenska
Prospective Opra Study And Report On
University Hospital
Present Status
A Translational Study Of The Neoplastic
Isabella Mak, MSc
Cells Of Gct Following Neoadjuvant
McMaster University, Hamilton Ontario, Canada
Denosumab
8:45 AM
Paper 1
8:55 AM
Paper 2
9:05 AM
Paper 3
9:15 AM
Paper 4
9:25 AM
Paper 5
9:35 AM
Paper 6
9:45 AM
9:55 AM
Paper 7
Discussant: Dempsey Springfield, MD
10:15 AM
Break
MSTS Funded Multi-Institutional Research Projects
10:30 AM
10:45 AM
11:00 AM
The Prophylactic Antibiotic Regimens In
Tumor Surgery (Parity) Multicenter
Randomized Controlled Trial: Moving From
The Pilot To The Definite Phase And
Michelle Ghert, MD, FRCSC
Lessons Learned Along The Way
McMaster University, Hamilton Ontario, Canada
Paper 8
Ct-Based Structural Rigidity Analysis Is
More Accurate Than Mirels Scoring System
For Fracture Prediction In Metastatic
Timothy Damron, MD
Femoral Lesions: Update On The Msts
SUNY Upstate Medical University Department of
Sponsored Study
Orthopedics, East Syracuse, NY
Paper 9
Panel Discussion: Ensuring Quality in Orthopaedic Oncology: What is the role of the MSTS?
Moderator: Kristy Weber, MD
Speakers: Robert Quinn, MD, Mark Scarborough, MD
12:00 PM
Lunch & Learn: Informal Q&A with MSTS Seasoned Professionals
Session II: Primary Bone Tumors
Moderators: Patrick Lin, MD, Parker Gibbs, MD
Cause-Specific Survival Improves Over
Time In Patients With Chondrosarcoma
1:00 PM
Paper 10
1:10 PM
Paper 11
1:20 PM
Paper 12
1:30 PM
Paper 13
Kyle Duchman, MD
University of Iowa, Iowa City, IA
Justin Bird, MD
Chondrosarcoma Of The Sacrum: A Review University of Texas MD Anderson Cancer Center,
Of 28 Cases At A Single Institution
Houston, TX
Osteoclast Inhibition Impairs Growth Of
Chondrosarcoma In Bone And Prevents
Jesse Otero, MD, PhD
Tumor-Mediated Bone Loss
University of Iowa, Iowa City, IA
2:00 PM
2:10 PM
The Regulation Of Etv5 By Sox9 And Mirna
In Human Chondrosarcoma
Patient Reported Quality Of Life And
Functional Outcomes After Sacrectomy For
Chordoma
Paper 14
Effect Of Surgical Margins On Disease-Free
Survival In Extremity, Non-Metastatic, HighGrade Osteosarcoma
Paper 15
Tumoral TP53 And/Or CDKN2A Alterations
Are Not Reliable Prognostic Biomarkers In
Patients With Localized Ewing Sarcoma: A
Report From The Children’s Oncology
Group
Paper 16
Discussant: John Healey, MD, FACS
2:30 PM
MSTS Member Business Meeting
MSTS Members Only (Active, Associate, Affiliate, Candidate, Resident, Emeritus can attend)
1:40 PM
1:50 PM
Isabella Mak, MSc
McMaster University, Hamilton Ontario, Canada
Rishabh Phukan
Massachusetts General Hospital, Boston, MA
Todd Bertrand, MD
H. Lee Moffitt Cancer Center and Research
Institute, Tampa, FL
Daniel Macht Lerman, MD
Huntsman Cancer Institute, University of Utah,
Salt Lake City, UT
Case Presentations
3:30 PM
4:30 PM
5:00 PM
7:00 - 10:00 PM
Moderator: Valerae Lewis, MD
Speakers: Carol Morris, MD, Peter Rose, MD, Douglas Letson, MD
Eugenie Kleinerman, MD
Aerosol Therapy for the Treatment of Osteosarcoma Lung
Professor and Head of the Division of Pediatrics,
Metastases
MD Anderson Cancer Center
Adjourn
Social Event
Saturday, October 11, 2014
7:00 - 8:00 AM
7 AM - 1:00 PM
7:00 AM - 12:30 PM
7:30 AM
Breakfast
Registration
Poster/Technical Exhibits
Welcome
Valerae Lewis, MD
Session III: Metastatic Disease, Lymphoma, and Multiple Myeloma
Moderators: Ginger Holt, MD, Justin Bird, MD
The Treatment Of Diaphyseal Femur
Fractures In Metastatic Renal Cell
Carcinoma
7:40 AM
Paper 17
Chapman Cadell
University of Texas MD Anderson Cancer Center,
Houston, TX
7:50 AM
Paper 18
8:00 AM
Paper 19
Predictors Of Reoperations And
Complications After Operative Treatment
For Metastatic Femur Fractures.
Targeting Skeletal Metastases Using HPMA
Copolymer Nanoparticle Delivery and
Retention
8:10 AM
Paper 20
Does Radiation Therapy Affect Survival And Yale Fillingham, MD
Functional Outcomes Of Non-Hodgkin
Department of Orthopaedic Surgery, Rush
Lymphoma Of Bone?
University Medical Center, Chicago, IL
8:20 AM
Paper 21
8:30 AM
Paper 22
8:40 AM
Paper 23
Discussant: Mark Gebhardt, MD
Pathology Unknowns
Best Poster Award
Break
Poster Session
8:50 AM
9:10 AM
9:50 AM
10:15 AM
Parathyroid Hormone Transiently Protects
Bone From Radiotherapy-Induced Damage
The Accuracy And Clinical Utility Of
Intraoperative Frozen Section Analysis In
Open Biopsy Of Bone
Influence Of Mesenchymal Stromal Cells On
Pulmonary Metastasis And Local
Recurrence In A Murine Model Of Minimal
Residual Disease Following Amputation Of
Primary Osteosarcoma
Stein Jasper Janssen, MD
Massachusetts General Hospital and Brigham
and Women's Hospital, Harvard Medical School
Alexander Christ, MD
Memorial Sloan Kettering Cancer Center, New
York, NY
Megan Oest, PhD
SUNY Upstate Medical University, Syracruse, NY
Matthew Wallace, MD
University of Texas MD Anderson Cancer Center,
Houston, TX
Nicole Ehrhart, VMD, MS
Colorado State University, Fort Collins, CO
Session IV: Soft Tissue Tumors
Moderators: Timothy
11:15 AM
Paper 24
11:25 AM
Paper 25
11:35 AM
Paper 26
11:45 AM
Paper 27
11:55 AM
Paper 28
12:05 PM
Paper 29
Does Obesity Effect Soft-Tissue Sarcoma
Outcomes?
Obesity Does Not Affect Survival Outcomes
In Extremity Soft Tissue Sarcoma
Magnetic Resonance Guided High Intensity
Focused Ultrasound: A Novel Noninvasive
Technique To Treat Soft Tissue Tumors Of
The Extremity
Transcutaneous Oximetry Can Predict
Wound Healing In Preoperatively Radiated
Soft Tissue Sarcoma
MRI Can Be Used To Risk Stratify Patients
With Extra-Abdominal Desmoid
Fibromatosis
Non-Radiographic Risk Factors
Differentiating Atypical Lipomatous Tumors
And Lipomas
Medical Malpractice And Sarcoma Care
–Who Is At Risk And Why Does It Occur?
12:15 PM
12:25 PM
Paper 30
Discussant: Steven Gitelis, MD
12:45 PM
Young Investigator Award
1:00 PM
Meeting Adjourns
Corey Montgomery, MD
University of Arkansas Medical Sciences, Little
Rock, AR
Ginger Holt, MD
Vanderbilt Medical Center, Nashville, TN
Raffi Avedian, MD
Stanford University, Redwood City, CA
Lukas Nystrom, MD
University of Iowa, Iowa City, IA
Behrang Amini, MD, PhD
University of Texas MD Anderson Cancer Center,
Houston, TX
Lee Morse, MD
University of Texas MD Anderson Cancer Center,
Houston, TX
Nathan Mesko, MD
Vanderbilt Orthopaedic Institute, Nashville, TN
Thank you for attending the 2014 MSTS Annual Meeting. We appreciate your feedback. Please complete the online evaluation linked
here .Contact [email protected] if you have any questions or additional comments you wish to share.
SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 1
LONG TERM OUTCOMES OF ENDOPROSTHETIC RECONSTRUCTION FOR PERIARTICULAR
TUMORS OF THE KNEE
Authors: Matthew T. Houdek, Benjamin K. Wilke, Eric R. Wagner, Cody C. Wyles, Franklin H. Sim
Institution: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
Introduction: In order to achieve an oncological margin during limb salvage surgery for tumors
around the knee, part or the entire knee joint is frequently sacrificed. Modular total knee
components are an option for reconstruction of the limb to restore a functional extremity and
achieve limb salvage. Although these prostheses are commonly used to restore function, there
continues to be a paucity of data concerning the risk factors for failure and overall long-term
outcomes.
Materials and Methods: Using our institutions total joint registry, we identified 215 patients
who underwent an endoprosthetic reconstruction for an oncological process effecting either the
distal femur and/or proximal tibia between 1972-2013. Kaplan-Meier survival outcomes and
Hazard ratios were assessed with a focus on need for reoperation, infection, and revision total
knee arthroplasty at an average follow-up of 6.2 years. Mean age was 41 years (range 8-88) at
the time of the reconstruction, with 55% being female. Fifty-one percent of patients were
classified as obese. The most common pathology at tumor extirpation was osteosarcoma
(n=95, 44%). Overall revision free survival was compared to 20,643 patients undergoing TKA for
degenerative joint disease (DJD) during the same time period.
Results: The mean 5-, 10-, 15- and 20-year revision free survival for an endoprosthetic
reconstruction following a periarticular knee resection was 76%, 62%, 49% and 37%, respectively
(Fig. 1). This was significantly worse (p<0.0001) than patients undergoing TKA for degenerative
joint disease, where 5-, 10-, 15- and 20-year survival was 96%, 90%, 82% and 74%, respectively
(Fig. 1). The mean time to revision total knee, reoperation for any cause and postoperative
infection were 6.2, 3.5 and 2.7 years. Amputation occurred in 13 patients, at a mean time of
4.3 years following reconstruction, with overall limb survival of 88% at 20-years. Hazard ratios
showed that patients with osteosarcoma were at increased risk for reoperation and infection.
Patient with postoperative complications including hematoma, delayed wound healing and
limited motion were at increased risk for reoperation. Likewise, patients who had delayed
wound healing were also at increased risk for infection (Table 1). Additional postoperative
complications included periprosthetic fracture (n=15, 6.9%), DVT/PE (n=4, 1.8%), and
component loosening (n=26, 12%).
Discussion: The results of this study show that revision surgery following periarticular knee
resection is high. Patients with a diagnosis of osteosarcoma are at increased risk of reoperation
and infection following reconstruction. Patients with postoperative complications such as
hematoma, limited motion and wound healing difficulty are at increased risk for reoperation;
however this did not increase the risk of revision surgery. Over the course of the 20-year
period, limb salvage was achieved in a majority of patients, with amputation only occurring in
12% of the patient population.
Disclosure information may be found on pages 51-60.
Table 1: Hazard Ratios for Revision, Reoperation and Postoperative Infection Following
Endoprosthetic Reconstruction of the Knee
Preoperative
Factors
Obesity
Male Gender
Age ≤40
Osteosarcoma
Chondrosarcom
a
Giant Cell
Tumor
Metastatic
Disease
Post-Operative
Complications
Hematoma
Delayed Healing
Limited Motion
Revision
TKA
(95% CI)
0.96
(0.33-2.29)
1.42
(0.87-2.29)
1.26
(0.76-2.14)
1.44
(0.89-2.36)
1.06
(0.44-2.18)
0.70
(0.35-1.29)
1.05
(0.31-2.69)
1.98
(0.48-5.46)
0.60
(0.14-1.62)
1.00
(0.47-1.89)
p
Value
Reoperation
(95% CI)
0.99
(0.47-1.87)
0.98
(0.66-1.45)
1.23
(0.82-1.85)
1.70
(1.15-2.53)
0.98
(0.49-1.76)
0.67
(0.37-1.16)
0.79
(0.35-1.55)
0.94
0.15
0.36
0.13
0.87
0.27
0.91
0.29
0.35
0.99
p
Value
0.98
0.95
0.31
0.007
0.96
0.16
0.52
2.58
(1.07-5.21)
9.10
(4.67-16.82)
2.07
(1.26-3.27)
Postoperative
Infection (95%
CI)
0.51
(0.08-1.79)
1.29
(0.34-1.72)
1.53
(0.67-3.75)
2.53
(1.12-6.22)
1.59
(0.46-4.17)
0.67
(0.15-1.98)
0.35
(0.01-1.75)
0.03
<0.00
01
0.004
1.22
(0.06-5.85)
5.49
(1.99-13.09)
2.09
(0.81-4.83)
p
Value
0.33
0.52
0.32
0.02
0.42
0.51
0.25
0.85
0.002
0.12
Figure 1: Overall Survival of Endoprosthetic Reconstruction of the Knee
DJD
Oncological Process
Disclosure information may be found on pages 51-60.
SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 2
RETROSPECTIVE EVALUATION OF THE INCIDENCE OF EARLY PERIPROSTHETIC
INFECTION WITH SILVER-TREATED ENDOPROSTHESIS IN HIGH RISK PATIENTS: CASE
CONTROL STUDY
Authors: Krishna I A Reddy, FRCSEd (Tr & Orth), Senior Oncology Fellow; Hazem Wafa,
FRCSEd(Tr & Orth), Consultant Orthopaedic Surgeon; Robert Grimer, FRCS, Consultant
Orthopaedic Surgeon; Adesegun Abudu, FRCS, Consultant Orthopaedic Surgeon; Lee Jeys,
FRCS, Consultant Orthopaedic Surgeon; Simon Carter, FRCS, Consultant Orthopaedic
Surgeon; Roger Tillman, FRCS, Consultant Orthopaedic Surgeon
Institution: The Royal Orthopaedic Hospital Oncology Service, The Royal Orthopaedic
Hospital NHS Trust, Birmingham, UK. Bristol Road South, Birmingham, B31 2AP
Abstract: The aim of this study is to compare the incidence of early periprosthetic infection
in high-risk patients who have undergone endoprosthetic reconstruction using the Agluna
silver-treated Stanmore custom endoprostheses with a control group who received a non
Agluna-treated Stanmore implants.
Methods: We conducted a case control study recruiting 85 patients with Agluna-treated
implants and 85 controls. There were 106 males and 64 females with a mean age of 42.2
years (range, 18.4 to 90.4 years) at the time of implant insertion. Fifty patients (29.4%)
received their implants for primary reconstruction, seventy-nine (46.5%) for one-stage
revision, while the remaining forty-one patients (24.1%) had a two-stage revision surgery for
periprosthetic infection. Endoprosthetic replacements were of the distal femur (n=63),
proximal tibia (n=36), proximal femur (n=19), hemipelvis (n=16), total femur (n=6), proximal
humerus (n=6), distal humerus (n=2), distal radius (n=2), intercalary (n=12), while eight
patients had combined femoral and tibial implants.
Results: All patients were followed up for a minimum of 6 months. Data collected during the
postoperative period, and at 3, 6, 9, and 12 month post-operative visits was analyzed. The
overall postoperative infection rates of the silver and control groups were 11.8% and 22.4%
respectively (p <0.05). Seven of the ten infected prostheses (70%) in the silver group were
successfully treated with debridement, antibiotics, and implant retention (DAIR) as
compared to only six of the nineteen infected implants (31.6%) in the control group (p
<0.05). Three patients with silver-treated implants (3.5%) and thirteen of the control group
(15.3%) had chronic periprosthetic infection necessitating device removal, amputation or
chronic antibiotic suppression (p <0.05). Six of the fifteen patients (40%) with positive
intraoperative cultures in the control group had postoperative infection versus only two of
the fifteen patients (13.3%) in the silver group (p <0.05). The overall success rates in
controlling infection with two-stage revisions in the silver and control groups were 85% and
57.1% respectively (p <0.05).
Conclusions: The Agluna-treated endoprostheses are associated with lower rates of early
periprosthetic infection. These silver-treated implants are particularly useful in two-stage
revisions for periprosthetic infection and in those patients with incidental positive cultures
at the time of implant insertion. The DAIR procedure appears to be more successful with
this type of implants.
Disclosure information may be found on pages 51-60.
SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 3
INFECTIONS IN MASSIVE BONE ALLOGRAFTS. MANAGEMENT AND RESULTS.
Authors: Luis A Aponte-Tinao MD, Miguel A Ayerza MD, D. Luis Muscolo MD and
German L Farfalli MD
Institution: Italian Hospital of Buenos Aires, Buenos Aires, Argentina
Abstract: The use of massive bone allografts implies the risk for infection. The purpose
of this study was to analyze a group of massive bone allografts analyzing the infection
rate, the management of this specific complication and the final outcome after this
complication.
We retrospectively reviewed 673 patients treated with massive bone allografts in long
bones between 1985 and 2011. There were 155 APC, 272 osteoarticular and 246
intercalary allografts from this study. Seventy-nine allografts were localized in the upper
limb and 594 in the lower limb (408 in femur and 186 in tibia). We analyzed the
infection rate, treatment of the complication and final outcome.
At final follow-up, 60 patients (9%) had an infection of the allografts. The infection rate
in APC was 12% (18 of 155 patients), 11% in osteoarticular (31 of 272 patients) and 5%
in intercalary (11 of 246 patients). Infection rate in the upper limb [4 of 79 patients (5%)]
was lower than in the lower limb [56 of 594 patients (9%)], however, if was similar if we
compare it only with femur allografts [25 of 408 patients (6%)]. The higher infection rate
was seen in tibia allografts [31 of 186 patients (16%)]. Eleven patients who had an
infection were treated with surgical debridement without removing the allograft. Fortynine infected allografts (82 per cent) were considered to be failures because amputation
of the limb (4 patients) or resection of the graft (45 patients) was required to control the
infection. In those patients we removed the allograft and implanted a temporary cement
spacer with antibiotics, and after infection control they were reconstructed with an
endoprosthesis in 17 cases and with a new allograft in 24 patients (11 APC, 5 intercalary
arthrodesis, 5 segmental intercalary and 3 osteoarticular). Four patients died of disease
with the cement spacer. In those 41 patients that were reconstructed, 14 failed due to a
second infection (34%)
The infection rate in this series was 9%. We found higher infection rate in tibia allografts
(16%). The failure rate of the infected allografts was 82% due to amputation or removal
of the graft. In those patients that a second reconstruction procedure was performed the
infection rate was of 34%.
Disclosure information may be found on pages 51-60.
SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 4
LATE COMPLICATIONS AND LONG-TERM OUTCOMES FOLLOWING REVISION OF A TOTAL
HIP ARTHROPLASTY PERFORMED FOR ONCOLOGICAL RESECTION
Authors: Matthew T. Houdek, Benjamin K. Wilke, Eric R. Wagner, Cody C. Wyles, Franklin H. Sim
Institution: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
Introduction: In order to achieve an oncological margin during limb salvage surgery for tumors
around the hip, part or the entire hip joint is frequently sacrificed. Total hip arthroplasty (THA)
is an option for reconstruction of the limb to restore a functional extremity and achieve limb
salvage. Although these prostheses are commonly used to restore function, due to various host
factors they can be fraught with complications and are commonly revised. Currently there is a
paucity of data concerning the late complications and long-term survival and risks of rerevision
following revision of a THA which was placed following an oncological resection.
Materials and Methods: Using our institutions total joint registry, we identified 53 patients
who underwent a revision of a THA which performed for an oncological process effecting either
the proximal femur or acetabulum from 1969-2006. Kaplan-Meier survival outcomes and
Hazard ratios were assessed with a focus on need for reoperation, infection, and rerevision
THA. All patients had least 5-years of follow-up, with a mean follow-up of 13.7 years (range 537). Mean age was 48 years (range 16-79) at the time of the revision, with 52% being female.
13% of patients were classified as obese. The most common pathology at tumor extirpation was
chondrosarcoma (n=11, 25%).
Results: The mean 10-, 15-, 20-, and 25-year revision free survival for an revision THA
following a THA for an oncological process of the hip was 88%, 69%, 38% and 29%, respectively
(Fig. 1). The mean time to rerevision THA, reoperation for any cause and postoperative
infection were 12.6, 10.5 and 6.4 years. Hazard ratios showed an increased risk for reoperation
in patients with dislocations (Table 1). There was a trend to an increased rate of revision in
younger patients, patients with metastatic disease and dislocation; however this was not
statistically significant (Table 1). Likewise there was no variable examined which statistically
increased the risk of infection (Table 1). Additional postoperative complications included
dislocation (n=10, 19.2%) periprosthetic fracture (n=8, 15.3%), DVT/PE (n=1, 1.9%), acetabular
wear (n=6, 11.5%) and component loosening (n=10, 19.2%).
Discussion: Late complications following revision surgery of a THA performed for an
oncological resection are common. In all the preoperative factors analyzed there was no
variable that was found to increase the risk of revision surgery; however patients with
acetabular wear, component loosing and periprosthetic were at increased risk for revision, as
expected. The results of this study provide valuable information that is useful in counselling
patients on what they should expect in the long-term about the survival and complications of a
revision THA in this difficult situation.
Disclosure information may be found on pages 51-60.
Table 1: Hazard Ratios for Rerevision, Reoperation and Postoperative Infection for Revision THA
Following THA for an Oncological Process of the Hip
Rerevision
Postoperative
Preoperative
p
Reoperation
p
THA
Infection (95%
p Value
Factors
Value
(95% CI)
Value
(95% CI)
CI)
0.56
0.59
Obesity
0.58
0.60
(0.02-3.47)
(0.03-3.25)
0.88
1.80
3.33
Male Gender
0.81
0.22
0.26
(0.32-2.52)
(0.71-4.92)
(0.42-67.34)
2.33
1.70
0.51
Age ≤40
0.10
0.26
0.53
(0.84-6.76)
(0.66-4.37)
(0.02-3.95)
1.48
2.49
Osteosarcoma
0.62
0.28
(0.22-5.78)
(0.38-9.31)
0.92
1.11
1.28
Chondrosarcoma
0.88
0.85
0.83
(0.25-2.69)
(0.31-3.15)
(0.06-10.07)
0.42
1.02
2.20
Giant Cell Tumor
0.22
0.97
0.52
(0.06-1.56)
(0.23-3.16)
(0.10-17.25)
3.64
0.94
Metastatic Disease
0.31
0.93
(0.18-22.5)
(0.14-3.36)
Allograft Prosthetic
1.91
1.19
0.44
0.82
Composite
(0.29-7.52)
(0.18-4.33)
Post-Operative
Complications
2.88
4.91
1.32
Dislocation
0.06
0.007
0.81
(0.96-1.03)
(1.59-14.25)
(0.06-10.37)
5.29
2.71
2.18
Acetabular Wear
0.005
0.06
0.53
(1.69-16.04)
(0.92-7.15)
(0.10-17.11)
Component
6.01
3.71
3.71
0.005
0.007
0.20
Loosening
(2.21-17.77)
(1.44-9.78)
(0.44-30.98)
Periprosthetic
6.79
2.64
2.13
0.009
0.09
0.54
Fracture
(1.70-24.42)
(0.82-7.47)
(0.10-16.76)
2.26
5.11
Infection
0.25
0.01
(0.50-7.30)
(1.39-15.36)
Figure 1: Overall Survival of Revision THA following THA for an Oncological Process Involving
the Hip
Disclosure information may be found on pages 51-60.
SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 5
TRANEXAMIC ACID DOES NOT INCREASE INCIDENCE OF DVT OR PTE IN SARCOMA
SURGERY
Authors: Herrick Siegel, MD, Jonathan Jennings, MD
Institutions: University of Alabama at Birmingham Medical Center
Abstract: Transexamic acid (TXA) has been reported to reduce the risk of bleeding and blood
transfusion in multiple subspecialties of orthopaedic surgery including spine and total joints.
There have been few reports in the literature evaluating the safety of its use in patients with
cancer. We report a consecutive series of soft tissue and bone sarcoma patients that were
administered tranexamic acid to reduce intraoperative blood loss and post op hematoma. This
study includes 38 sarcoma patients treated between January 2012 through December 2013 by a
single surgeon, all of whom were given 1 g of TXA pre op and at the time of closure. Exclusion
criteria because of a recent history of cardiac stent placement, pulmonary embolism and DVT.
Blood loss, transfusion incidence and symptomatic blood clots (DVT and PTE) were recorded.
The study group was then compared to a control group of total joint patients that were also
given the same TXA protocol to determine whether there was an increased risk of complications
in the study group. Additionally, blood loss and transfusion incidence was also compared to a
historical matched control group of sarcoma patients that were treated without TXA.
The incidence of blood clots (DVT and PTE) was not statistically significant between the sarcoma
and arthroplasty group. Two DVTs were noted in the arthroplasty group and one in the
sarcoma group (p=0.021). One PTE was seen in the arthroplasty group and none were noted in
the sarcoma group. Blood loss, post op hematoma incidence and transfusion rates were all
lower in the TXA sarcoma group; however statistical significance was not reached (p=0.077).
Tranexamic acid is safe and effective in sarcoma surgery. It is routinely used at our institution
on all sarcoma patient undergoing a wide resection, if blood loss greater than 200 cc is
anticipated. In those patients with relative contraindication to its use (recent cardiac stent,
history of DVT/PTE or renal failure), it is used topically in a diluted solution.
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SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 6
AN OSSEOINTEGRATED PERCUTANEOUS PROSTHETIC SYSTEM FOR TREATMENT OF
TRANSFEMORAL AMPUTEES: RESULTS FROM THE PROSPECTIVE OPRA STUDY AND
REPORT ON PRESENT STATUS
Authors: Örjan Berlin, MD, Ricard Brånemark, MD
Institution: Department of Orthopaedics, Sahlgrenska University Hospital, GOTHENBURG,
SWEDEN
Introduction: Recently we published the first prospective study on the results of boneanchored amputation prostheses in transfemoral amputees (TF amp) (Bone Joint J 2014;96B:106-113). We report on the continuous follow-up of the results of this technique.
Methods: The surgery consists of a two-stage procedure. First a titanium screw (fixture) is
inserted into the remaining skeleton (S1 operation). Six months later a second implant
(abutment) is inserted into the first, allowing it to penetrate the skin (S2 operation). The
abutment has a press-fit area into the fixture and the two components are secured by an
abutment screw (As). Gradual increase of loading are done over a 6-month period.
Results: The OPRA study includes 51 patients with 55 implants (1999–2008). Follow up is 2
years (May 2010) and 5 years (May 2013). At the 2 year follow-up four implants had been
removed due to loosening (3) or infection (1). The implant survival was 92 % (48/52). The
patients had an average of one superficial infection every two years, successfully treated
conservatively in all cases. There were 6 deep infections in 4 patients. All but one were
successfully treated by conservative means. Four patients had 9 mechanichal complications
(bent or fractured implant parts) and 3 skeletal fractures occurred. Prosthetic use, prosthetic
functions and global quality of life were all significantly improved (p<0.001). In May 2013
the 5-year follow-up data were gathered showing an increased risk for mechanical problems
(especially with the As), however the absolute majority of them could be managed and
solved through ”service” operations. The incidence of infections are under analysis and need
further definitions since asymptomatic bacterial colonisation of the bony canal can occur,
without signs of overt deep infection and with no significant dysfunction for the patient.
Gradual improvement of the surface of the implants (Biohelix structure®) with
nanotechnology studies have improved the mechanical strength of the bony ingrowth onto
the fixture.
Conclusions: The implementation of a standardized osseointegrated surgical technique and
the graded rehabilitation protocol is of importance for the promising results. The amputee
no longer has skin ulcers, pain when loading, and problems with stump volume changes.
Normal sitting comfort and normal hip range of motion can be expected. All these changes
lead to a significantly improved quality of life for patients with an oseointegrated prosthesis
after a TF amputation. The As is the weak point of the system, but also allows service
operations after long use. The long-term complication rate need to be continuously carefully
monitored.
(n=411)
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SESSION I: PROSTHESIS AND ALLOGRAFTS
Friday, October 10, 2014 | 8:45 AM – 10:15 AM
PAPER 7
A TRANSLATIONAL STUDY OF THE NEOPLASTIC CELLS OF GCT FOLLOWING NEOADJUVANT
DENOSUMAB
Authors: Nathan Evaniew, MD, Isabella Mak, BS, MsC, Snezana Popovic, Richard Tozer, Michelle
Ghert. MD, FRCSC
Institution: McMaster University, Hamilton, Ontario, Canada
Objectives: Giant Cell Tumor of Bone (GCT) is a primary bone tumor that is treated surgically
and in many cases is associated with high morbidity. Until recently, there were no established
adjuvant systemic treatment options for patients with extensive or unresectable GCT. GCT
consists of osteoclast-like giant cells that express Receptor Activator of Nuclear factor-κB
(RANK) and mononuclear stromal cells that express RANK ligand (RANKL). The functional
interaction between the stromal-cell derived RANKL and the osteoclast receptor (RANK) results
in a steady production of osteoclast-like cells in the tumor that are responsible for resorbing
bone. Denosumab is a monoclonal antibody that binds RANKL and directly inhibits
osteoclastogenesis. Clinical studies have suggested clinical and histological improvement when
Denosumab was administered to patients with GCT. However, no studies have yet examined the
viability of the neoplastic stromal cells once the cells are no longer exposed to Denosumab.
Materials and Methods:
GCT sample collection: Specimens were obtained at the time of biopsy from six patients with
histologically confirmed GCT. Two of the GCT patients then went on to be treated with
preoperative Denosumab. Standard paraffin-embedded haematoxylin and eosin (H+E)
examination was used for both the biopsy and resection specimens.
Primary cell lines and culture: Primary cell cultures of GCT stromal cells were isolated,
characterized and established from the fresh GCT patient tissue at the time of definitive
resection. Fifth passage cells were used for in vitro experiments.
WST-1 cell proliferation measurement: Mitochondrial dehydrogenase activity, as an indicator of
cell number, was assessed by the mitochondrial-dependent reduction of WST-1 to formazan
using a colorimeter at indicated time-points over a 2-day time course.
RNA purification, reverse transcription and real-time polymerase chain reaction (PCR): Total RNA
was isolated from GCT stromal cells and single-stranded complementary DNA (cDNA) was
synthesized from 1.0µg of total RNA and applied to real-time PCR. The expression of RANKL
and OPG was analyzed using real-time RT-PCR. PCR experiments were performed in triplicate
and included negative no-template controls.
Results: Histological specimens from both patients who were treated with Denosumab showed
the absence of giant cells, but with persistent stromal cells. WST-1 cell proliferation studies
indicated that GCT stromal cells cultured from clinical specimens exposed to Denosumab
proliferated at a ~50% slower rate compared to specimens not exposed to Denosumab.
Furthermore, the expression of RANKL in post-Denosumab GCT specimen was eliminated. In
contrast, osteoprotegerin (OPG), the decoy receptor of RANKL, was upregulated over several
hundred fold.
Conclusions: The current report confirms that once the remaining GCT tissue is no longer
exposed to Denosumab, the stromal cells continue to proliferate, albeit to a lesser degree. They
also show complete loss of expression of the osteoclastogenic factor RANKL. Based on the postDenosumab histological specimens reported by the current study and others, Denosumab
appears to be biologically active in inhibiting osteoclastogenesis, which would be expected of a
mononclonal antibody that binds RANKL. However, we have shown that once the
microenvironment is free of the antibody, the neoplastic cells remain proliferative but do not
express RANKL. It is clear that treatment with Denosumab only addresses the therapeutic need
of GCT partially by wiping out the osteoclasts but leaving the neoplastic stromal cells
proliferative.
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MSTS FUNDED MULTI-INSTITUTIONAL RESEARCH PROJECTS
Friday, October 10, 2014 | 10:30 AM - 11:00 AM
PAPER 8
THE PROPHYLACTIC ANTIBIOTIC REGIMENS IN TUMOR SURGERY (PARITY) MULTICENTER
RANDOMIZED CONTROLLED TRIAL: MOVING FROM THE PILOT TO THE DEFINITE PHASE
AND LESSONS LEARNED ALONG THE WAY
Authors: The PARITY Investigators (please see following page for full list)
Background: PARITY is a multi-center, randomized controlled trial in which patients with a
tumor of the lower extremity and who are undergoing endoprosthetic reconstruction are
randomized to one of two study arms: 1 day of post-operative antibiotics, or 5 days of
postoperative antibiotics. The study is coordinated by the Center for Evidence-Based
Orthopaedics at McMaster University and opened to pilot phase enrolment in 2013. The
following is an update of the trial progress, the transition to the definitive phase, and lessons
learned in this prospective multi-center MSTS-funded initiative.
Methods: PARITY patients are randomized by the pharmacy team at each clinical site through
an online randomization program. Patients, surgeons, nurses, study coordinators, analysts,
adjudicators and the research team are blinded to treatment allocation. The primary outcome is
rate of surgical site infection according to a survival analysis, and outcomes assessment is
adjudicated by the PARITY Adjudication Committee through a secure online platform. Data are
monitored for patient safety by an independent Data Safety and Monitoring Board, and data
quality is screened at regular intervals to maintain high standards of data quality.
Results: Funding for the PARITY study pilot feasibility phase was awarded by the OREF/MSTS,
the Physicians’ Services Incorporated Foundation, and the Canadian Cancer Society Research
Institute. At the time of abstract submission, a total of 41 patients have been randomized
across 15 sites in the United States, Canada, Argentina, and Australia. A further 5 sites in the
United States are opening to enrollment in June 2014. There are 15 additional sites currently in
the active start-up phase (contract negotiations and ethics applications) across Canada, the
United States, England, Scotland, Denmark, Finland and India. In total, 55 clinical sites across
17 countries and 5 continents are participating or have expressed interest in PARITY. The
definitive phase of PARITY will complete enrolment of the sample size of 600 patients, for
which funding has been requested from the National Cancer Institute and the Canadian
Institutes of Health Research. Several challenges of multi-center, international collaboration
have been encountered, including: executing institutional contracts, obtaining ethics approvals,
translating study material into different languages, managing variances in available antibiotics,
and working within national regulatory requirements. Each of these challenges has been
overcome by strong investigator and research personnel support, a cohesive collective effort of
the MSTS, and by a desire to enhance patient care through an evidence-based approach.
Conclusion: PARITY is the first international, prospective, randomized collaborative study in
orthopaedic oncology. With the support of the MSTS, the pilot phase is nearing completion and
has generated substantial international momentum. Preparations to transition to the definitive
phase of PARITY are underway. The expanding group of PARITY Investigators has demonstrated
the feasibility of conducting a large surgical trial and of establishing a successful trials network
in orthopaedic oncology.
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MSTS FUNDED MULTI-INSTITUTIONAL RESEARCH PROJECTS
Friday, October 10, 2014 | 10:30 AM - 11:00 AM
PARITY Investigators
Enrolling
Dr. Michelle Ghert (Juravinski Hospital and Cancer Centre / Hamilton, ON)
Dr. Peter Ferguson / Dr. Jay Wunder (Mount Sinai Hospital / Toronto, ON)
Dr. Robert Turcotte (McGill University Health Centre / Montreal, QC)
Dr. Marc Isler / Dr. Sophie Mottard (Hôpital Maisonneuve-Rosemont / Montreal, QC)
Dr. Paul Clarkson (Vancouver General Hospital / Vancouver, BC)
Dr. Joel Werier (The Ottawa Hospital – Ottawa, ON)
Dr. Norbert Dion (Hôtel Dieu du Quebec – Quebec City, QC)
Dr. Ginger Holt (Vanderbilt Medical Center – Nashville, TN)
Dr. R. Lor Randall (Huntsman Cancer Institute – Salt Lake City, UT)
Dr. John Healey (Memorial Sloan-Kettering Cancer Center – New York City, NY)
Dr. Megan Anderson / Dr. Mark Gebhardt (Boston Children’s Hospital / Beth Israel Deaconess
Medical Center – Boston, MA)
Dr. Tessa Balach (University of Connecticut Health Center – Farmington, CT)
Dr. Edward Cheng (University of Minnesota Medical Center – Minneapolis, MN)
Dr. Benjamin Miller (Holden Comprehensive Cancer Center – Iowa City, IO)
Dr. Thomas Scharschmidt (Wexner Medical Center – Columbus, OH)
Dr. Nickolas Reimer (Emory University Orthopedics and Spine Center – Atlanta, GA)
Dr. Raffi Avedian (Stanford University Hospital and Clinics – Redwood City, CA)
Dr. John Abraham (The Rothman Institute – Philadelphia, PA)
Dr. Mark Clayer (Royal Adelaide Hospital – Adelaide, Australia)
Dr. Marcos Galli Serra (Hospital Universitario Austral – Buenos Aires, Argentina)
Start-Up
Dr. Shannon Puloski (Foothills Medical Centre – Calgary, AB)
Dr. Lukas Nystrom (Cardinal Bernardin Cancer Centre – Chicago, IL)
Dr. David Geller (Montefiore Medical Center – Bronx, NY)
Dr. Yee-Cheen Doung / Dr. James Hayden (Oregon Health & Science University Hospital –
Portland, OR)
Dr. Joseph Schwab (Massachusetts General Hospital – Boston, MA)
Dr. Howard Goodman (Maimonides Medical Center – Brooklyn, NY)
Dr. Kurt Weiss / Dr. Mark Goodman (University of Pittsburgh Medical Center – Pittsburgh, PA)
Dr. Albert Aboulafia (Franklin Square Medical Center / Sinai Hospital of Baltimore – Baltimore,
MD)
Dr. Robert Grimer (The Royal Orthopaedic Hospital NHS Foundation Trust – Birmingham, United
Kingdom)
Dr. Sander Dijkstra (Leiden University Medical Centre – Leiden, Netherlands)
Dr. Minna Laitenen (University Hospital of Tampere – Tampere, Finland)
Dr. André Mathias Baptista (São Paulo, Brazil)
Dr. Shah Alam Khan (All India Institute of Medical Sciences – New Delhi, India)
Dr. Ajay Puri (Tata Memorial Centre – Mumbai, India)
Actively Interested
Dr. Emily Carmody Soni (University of Rochester Medical Center – Rochester, NY)
Dr. Judd Cummings (Phoenix Children’s Hospital – Phoenix, AZ)
Dr. Timothy Damron (SUNY Upstate University Hospital – East Syracuse, NY)
Dr. Cynthia Kelly (The Denver Clinic for Extremities – Denver, CO)
Dr. Yair Gortzak (Tel Aviv Medical Centre – Tel Aviv, Israel)
Dr. Werner Hettwer (Righospitalet – Copenhagen, Denmark)
Dr. Paul Jutte (University Medical Center Groningen – Groningen, Netherlands)
Dr. Tom Beckingsale (Newcastle upon Tyne Hospital – Newcastle, United Kingdom)
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MSTS FUNDED MULTI-INSTITUTIONAL RESEARCH PROJECTS
Friday, October 10, 2014 | 10:30 AM - 11:00 AM
PAPER 9
CT-BASED STRUCTURAL RIGIDITY ANALYSIS IS MORE ACCURATE THAN MIRELS
SCORING SYSTEM FOR FRACTURE PREDICTION IN METASTATIC FEMORAL LESIONS
Authors: Timothy A. Damron, MD4; Ara Nazarian, PhD.1; Vahid Entezari, MD1; Carlos
Brown, MD4, William Grant, Ed.D.13, John A. Hipp, PhD.2; Nathan Calderon, MSc.2; David
Zurakowski PhD3, Richard M. Terek, MD5; Megan E. Anderson, MD6; Edward Y. Cheng,
MD7; Felix Cheung, MD8; Albert J. Aboulafia, MD9; Robert Turcotte, MD10; Patrick P. Lin
MD11, Mark C. Gebhardt, MD6; Brian D. Snyder, MD, PhD1,12
Institutions:
Center for Advanced Orthopaedic Studies, Department of Orthopaedic Surgery, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
2
Baylor College of Medicine, Houston, TX
3
Departments of Anesthesiology, General Surgery and Orthopaedic Surgery, Children’s
Hospital, Harvard Medical School, Boston, MA, USA
4
Department of Orthopedic Surgery, Upstate Medical University, Syracuse, NY
5
Department of Orthopaedic Surgery, Rhode Island Hospital, Providence, RI
6
Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA
7
Department of Orthopaedic Surgery, University of Minnesota Medical Center,
Minneapolis, MN
8
Edwards Comprehensive Cancer Center, Huntington, WV
9
Department of Orthopaedic Surgery, Sinai Hospital, Baltimore, MD
10
Department of Orthopaedic Surgery, McGill University Health Centre
11
Section of Orthopaedic Oncology, University of Texas M. D. Anderson Cancer Center,
Houston, TX
12
Department of Orthopaedic Surgery, Children’s Hospital Boston, Harvard Medical
School, Boston, MA
13
Biostatistics, Department of Emergency Medicine, Upstate Medical University,
Syracuse, NY
1
Background: Controversy continues regarding the appropriate assessment of fracture
risk in long bone lesions affected by disseminated malignancy. The purpose of this
ongoing Musculoskeletal Tumor Society (MSTS) sponsored, multi-institutional
prospective cross-sectional clinical study is to compare CT-based Structural Rigidity
Analysis (CTRA) to physician-derived Mirels scoring for predicting pathologic fracture in
femoral bone lesions.
Methods: Enrollment to date is 138 patients with 169 lesions. Patients underwent CTRA
analysis and were assigned Mirels scores by the treating surgeon. Of the 138 patients,
36 patients (38/169 lesions) underwent prophylactic fixation, 33 patients (47/169
lesions) had not completed 1 year follow-up, and 6 dropped out (losing 7/169 lesions).
The remaining 63 patients (77 lesions), who did NOT undergo prophylactic stabilization,
qualified for the current analysis. Endpoints were (1) completion of 12-month follow-up
without fracture (30 pts), (2) pathologic fracture through the lesion at risk (6 pts), or (3)
death without fracture (27 pts).
Results: All six fractures occurred within the first 4 months after initial CTRA evaluation
and were correctly predicted by CTRA and Mirels scoring of >8, but only 4 of 6 were
predicted using a Mirels score of 9 or 10 as the threshold impending fracture. CTRA
provided higher sensitivity (100% vs 67%), specificity (61% vs 48%), positive predictive
value (17.6% vs 9.8%) and negative predictive value (100% vs 94.4%) compared to the
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classic Mirels definition of impending fracture (> 9). ROC analysis also indicated CTRA to
be significantly more accurate than the classic Mirels definition of impending fracture.
Conclusions: CT-based structural rigidity analysis has better sensitivity, specificity and
positive and negative predictive value than Mirels using the classic threshold of 9 points
as the definition of an impending pathologic fracture. Further, CTRA provided overall
good accuracy of prediction, whereas Mirels score >9 was no better than chance. CTRA
appears to provide a substantial advance in the accuracy of predicting pathological
femur fracture over the current clinical and radiographic criteria.
Level of Evidence: II
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 10
CAUSE-SPECIFIC SURVIVAL IMPROVES OVER TIME IN PATIENTS WITH CHONDROSARCOMA
Authors: Kyle R. Duchman MD1, Charles F. Lynch MD, MS, PhD2, Joseph A. Buckwalter MD, MS1,
Benjamin J. Miller MD, MS1
Institution: 1Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and
Clinics; 2Department of Epidemiology, University of Iowa College of Public Health
Introduction: Conditional survival measures change in the risk of mortality given that a patient
has survived a defined period of time. This has yet to be reported for chondrosarcoma of bone.
The purpose of this study is to determine whether the cause-specific survival for
chondrosarcoma improves with each additional year of survival after diagnosis while
considering tumor stage, location, patient age, and use of radiation therapy in the treatment
regimen.
Methods: We used the Surveillance, Epidemiology, and End Results Program database
maintained by the National Cancer Institute to identify 2138 patients with chondrosarcoma of
bone from 1973 to 2009. We used an actuarial life table analysis to explore differences in 5year cause-specific survival estimates conditional on 1 to 5 years of survival. The cohort was
stratified by grade, location (axial versus extremity), use of radiation, and age.
Results: The estimated survival for all grades of local/regional chondrosarcoma improved from
baseline with each year of survival after diagnosis. At 5 years after diagnosis, local/regional
Grade 1 chondrosarcoma displayed higher conditional survival than Grade 2 and 3
local/regional chondrosarcoma (97.2% versus 92.8%, p = 0.006 and 97.2 versus 83.8%, p =
0.012). Estimated survival improved from baseline with each year of survival for all grades of
metastatic chondrosarcoma. Conditional survival estimates for Grade 3 axial tumors failed to
improve from baseline to 5 years after diagnosis (52.9% versus 70.2%, p = 0.15) compared with
Grade 3 extremity tumors at baseline and 5 years after diagnosis (58.1% versus 95.8%,
<0.0001) The 20-year conditional survival estimates reveal that a cancer-specific risk of
mortality exists even 10 years after diagnosis, suggesting that although the conditional survival
increases considerably over time, it cannot be considered cured.
Conclusions: The 5-year conditional survival estimate for patients with chondrosarcoma
improved with each additional year of survival regardless of grade, site, age, or use of radiation.
At 10 years after diagnosis, deaths attributable to cancer were still present, and patients should
be aware of this small long-term risk.
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 11
CHONDROSARCOMA OF THE SACRUM: A REVIEW OF 28 CASES AT A SINGLE INSTITUTION
Authors: Justin Bird, MD, Valerae Lewis, MD, Joel Zarling, MD, Patrick Lin, MD, Bryan Moon, MD,
Robert Satcher, MD
Institution: University of Texas MD Anderson Cancer Center
Introduction: Approximately 5% of primary bone cancers involve the sacrum and mobile spine (ACS,
2008, M-SEER 1). Most data on sacral tumors include pooled histologies (Hsieh 2009; Fourney
2005), and are skewed towards chordomas. In a population-based study, however,
chondrosarcomas comprised the majority (34%) of the 1,351 sacral/pelvic tumors (Mukherjee 2011).
Our understanding of the site specific characteristics of sacral chondrosarcomas is limited because
we lack data evaluating this particular cohort. The purpose of this study was to evaluate outcomes
following surgical and adjuvant treatment of sacral chondrosarcomas.
Methods: We report data from a retrospective review of 28 patients with sacral chondrosarcomas
treated surgically at a single institution. Over a 22 year period (from 1992 to 2014) data were
collected on demographics, symptomatology, surgical and adjuvant therapies, pathology,
complications, recurrence and mortality. Recurrence, metastasis, and disease-free interval data were
calculated from the date of most recent surgery (or most recent adjuvant radiation or chemotherapy,
if applicable). Follow-up was determined from the date of the most recent intervention until the date
of the last documented clinical follow-up (if alive) or until the date of death. All cases with a
minimum of 2 years follow-up were included in the survival analysis.
Results: Twenty-eight patients with sacral chondrosarcoma underwent a combined eighty-four
surgical procedures. Three patients having less than 2 year follow-up were excluded from the
survival analysis. Of the patients with less than 2 years follow-up, one patient underwent a staged
partial sacrectomy/external hemipelvectomy and received chemotherapy for dedifferentiated
chondrosarcoma and is alive with no evidence of disease. The other two patients presented with
high grade disease, developed widely metastatic disease shortly after surgery, and are currently
receiving palliative care. Twenty-five patients had greater than 2 years follow-up. Of these, one case
was Grade 1, eleven were Grade 2, and 13 were Grade 3. The sole patient with grade 1
chondrosarcoma underwent a planned intralesional resection due to advanced age and died
secondary to other causes 24 months post-operatively with no evidence of local or metastatic
disease. Eleven Grade 2 chondrosarcoma patients (11/25) underwent 43 surgical procedures. Dural
tears complicated two procedures, wound dehiscence complicated another six. Of the eleven Grade
2 patients, eight (73%) were deceased, all secondary to either metastatic pulmonary disease or renal
complications due to local recurrence. Of the deceased, median survival was 129.4 months. Three
patients were alive with no evidence of disease at a mean follow-up of 64 months. Only one patient,
among the deceased, received adjuvant chemotherapy. Thirteen Grade 3 chondrosarcoma patients
(13/25) underwent twenty-eight procedures. Wound dehiscence complicated five cases. There were
2 dural tears and 2 cases complicated by hemorrhage. Mortality was forty-four percent (7/13), with
a median survival of twenty-seven months. Six patients with grade 3 chondrosarcomas received
chemotherapy, of whom, two were still alive at last follow-up.
Conclusion: The prognosis for chondrosarcoma of the sacrum is poor. Local control is difficult to
achieve and multiple procedures with high complications rates can be expected. When wide
resection is achieved it is associated with improved prognosis. Mortality is primarily due to either
pulmonary metastases or renal complications secondary to local disease.
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 12
Osteoclast Inhibition Impairs Growth of Chondrosarcoma in Bone and Prevents
Tumor-mediated Bone Loss
Authors: Jesse E. Otero MD PhD, Jeff W. Stevens PhD, Allison E. Malandra DVM, Douglas
C. Fredericks MS, Jose Morcuende MD PhD
Institution: University of Iowa
BACKGROUND: Chondrosarcoma (CHS) is an aggressive primary tumor of bone that is
resistant to chemotherapy and radiation treatment. Surgery is the mainstay of current
therapy, and survival is poor in patients with recurrent and metastatic disease. Cellular
and molecular mechanisms of pathogenesis in CHS remain elusive. Recent research has
implicated microenvironmental factors in the behavior of chondrosarcoma in bone. We
hypothesized that osteoclasts (OCs) in the microenvironment of CHS play a crucial role
in bone resorption and growth of the tumor in bone. The Swarm rat chondrosarcoma
(SRC) is a transplantable chondrogenic tumor with biological behavior that mimics CHS
in bone.
OBJECTIVE: The objective of our study was to document the presence and characterize
the activity of osteoclasts at the bone tumor interface, to determine the local effect of
tumor on bone, and to study the effect of inhibition of osteoclasts on tumor behavior.
METHODS: Three groups of rats were utilized in the study. One group received PBS
injections into the tail vein weekly for three weeks and then underwent SRC tumor
implantation into the right tibia. The contralateral tibia served as an internal control.
Another group of rats received weekly tail vein injections of zoledronic acid (ZA), an
osteoclast inhibitor, for three weeks before implantation of tumor into the right tibia.
The control group received PBS injection and sham surgery consisting of corticotomy
and wound closure. X rays were taken weekly, and animals were euthanized at day 21
post-operatively. Bilateral tibiae were analyzed by peripheral quantitative computed
tomography (pqCT) and were evaluated histomorphomerically for tumor growth,
osteoclast activation, and bone destruction. We also tested these parameters after tumor
implantation in a group of osteopetrotic rats, which genetically lack osteoclasts,
compared with normal littermate controls.
RESULTS: Implantation of SRC into tibia induced a massive osteolytic response in local
bone. There was a concomitant increase in osteoclast number and size compared with
sham tibiae. Osteoclast surface and resorbed surface was statistically greater in the
presence of tumor than in sham tibiae. Furthermore, pqCT showed a statistically
significant reduction in local bone mineral density in SRC-implanted tibiae than sham
tibiae (p=0.008). ZA increased bone mineral density and inhibited bone destruction in
the presence of SRC tumor. Osteoclasts appeared rounded and dysfunctional, and
resorbed bone surface was reduced compared with PBS-treated tumor-bearing tibiae.
There was a significant reduction in tumor volume within the intramedullary space of
ZA-treated tumor bearing tibiae than those treated with PBS. Additionally, tumor growth
was impaired in tibiae of osteopetrotic rats compared with littermate controls.
CONCLUSION: Data from our in vivo model suggests that osteoclasts contribute to local
bone destruction induced by CHS and enhance growth of CHS in bone. Modulation of OC
activity represents an attractive therapeutic strategy for local control of CHS growth.
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1. Donati D, El Ghoneimy A, Bertoni F, Di Bella C, Mercuri M. Surgical treatment and
outcome of conventional pelvic chondrosarcoma. J Bone Joint Surg Br. 2005
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2. Maibenco HC, Krehbiel RH, Nelson D. Transplantable osteogenic tumor in the rat.
Cancer Res. 1967 Feb;27(2):362-6.
3. Breitkreutz D, Diaz de Leon L, Paglia L, Gay S, Swarm RL, Stern R. Histological
and biochemical studies of a transplantable rat chondrosarcoma. Cancer Res.
1979 Dec;39(12):5093-100.
4. Grimaud E, Damiens C, Rousselle AV, Passuti N, Heymann D, Gouin F. Bone
remodelling and tumour grade modifications induced by interactions between
bone and swarm rat chondrosarcoma. Histol Histopathol. 2002 Oct;17(4):110311.
5. David E, Blanchard F, Heymann MF, De Pinieux G, Gouin F, Rédini F, Heymann D.
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2011;2011:932451.
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 13
THE REGULATION OF ETV5 BY SOX9 AND MIRNA IN HUMAN CHONDROSARCOMA
Authors: Isabella Mak, BS, MSc*, Robert Turcotte, MD^, Michelle Ghert, MD, FRCSC*
Institutions:
*McMaster University, Hamilton, ON, Canada
^McGill University Health Centre, Montreal, QC, Canada
Introduction: Chondrosarcoma is a malignancy of cartilage and is the most common primary
bone malignancy in the adult population. Chondrosarcoma is a unique bone sarcoma in that it
does not respond to chemotherapy or radiation treatment. Thus, survival rates in this patient
population are low with a high chance of developing lung metastases. Chondrosarcoma is
treated with surgical excision where feasible, often carrying a very high morbidity rate, and an
attempt at reconstruction. There exists a dire need to develop systemic treatments to target
chondrosarcoma cells and prevent metastatic spread. Our lab has previously shown that the
ability of malignant cartilage cells in chondrosarcoma to invade calcified bone matrix is due, at
least in part, to matrix metalloproteinase-2 (MMP-2), which is in turn regulated by its upstream
transcription factor, ETS transcript variant 5 (ETV5). It has been shown that the SRY-related
high-mobility group-Box gene 9 (SOX9) is an upstream regulator of ETV5 in kidney development,
as well as the master regulator of chondrogenesis. Epigenetic regulation of SOX9 may involve
microRNAs (miRNAs), specifically miR145. Therefore, we hypothesized that expression of SOX9
in chondrosarcoma cells leads to downstream activation of ETV5. In addition, we hypothesized
that miR145, which is known to downregulate SOX9, would be under-expressed in
chondrosarcoma cells.
Methods:
Cell cultures: The human chondrosarcoma cell lines JJ012 (JJ) and 105KC (KC) have been chosen
for the current proposal as they are human cells obtained from high-grade and invasive human
chondrosarcoma.
Immunofluorescence assays: Immunofluoresent assays were performed on chondrosarcoma
cells with the SOX9 mouse monoclonal antibody.
Transfection of the ETV5 construct: The ETV5 promoter-reporter construct (ETV5-LUC) was
generated by insertion of a ~1kb ETV5 promoter fragment into a luminescent reporter Gluc
vector.
Luciferase assay: Culture media were collected after transfection and the luciferase activities
were measured.
Co-transfection of SOX9 lentivirus & miR145 lentivirus: The SOX9-GFP CMV 3rd generation
lentiviral vector was amplified in bacteria, packaged in 293T cells, and infected in
chondrosarcoma cells which had already been transfected with the ETV5 construct. Culture
media were collected after transfection and detected with luciferase assays. Similar miR145
lentiviral transfection was performed on chondrosarcoma cells.
Real time PCR analysis: Cells were lysed and total RNA was extracted for real time PCR analysis.
The expression levels of SOX9 and ETV5 in chondrosarcoma cells transfected with the ETV5
promoter-reporter plasmid and SOX9 lentivirus were determined using real-time PCR as
previously described. miRNA expression levels in chondrosarcoma cells and 4 patient samples
were also determined by real time PCR. GAPDH & RNU48 were used for normalization.
Disclosure information may be found on pages 51-60.
Results: The expression of SOX9 in human chondrosarcoma cells was strongest within the
nucleus as demonstrated by in situ fluorescent immunocytochemistry. After transfecting
chondrosarcoma cells with the ETV5 promoter-reporter plasmid, luciferase activity of the ETV5
promoter was induced. In addition, co-transfection of the ETV5 promoter-plasmid with the
SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter
(P<0.05). In order to validate the lentivirus SOX9 regulation of the ETV5 promoter, expression
of ETV5 and SOX9 mRNA detected by real time PCR confirmed upregulation of ETV5 in SOX9
lentiviral transfected cells (P<0.05). The intrinsic level of miR145 in chondrosarcoma cells and
patient samples was significantly lower than that of RNU48 and chondrocyte control cell line.
Discussion: The clinical challenge for chondrosarcoma is to identify treatment options for
unresectable or metastatic disease. SOX9 plays a pivotal role in chondrocyte differentiation,
and it is over-expressed in chondrosarcoma. Since our lab has previously shown that ETV5 has
a significant role in regulating MMP2 expression, it is important to determine if SOX9 regulates
ETV5, resulting in matrix resorption in human chondrosarcoma. From the data of this study, it
is clear that SOX9 up-regulates ETV5 expression at the promoter region. Furthermore, the low
level of miR145 that we identified in chondrosarcoma may lead to a high expression of SOX9,
and therefore downstream invasion and metastasis in chondrosarcoma.
Significance: Results from this study would close the loop between the invasive properties of
chondrosarcoma and the upstream epigenetic regulation of SOX9. The expression of miR145 is
aberrantly low in chondrosarcoma, hence the lack of inhibition of SOX9, leading to downstream
activation of ETV5 and MMP2, and subsequent bone and matrix invasion. Several diseases are
currently being approached with therapeutic miRNA and therefore, the information generated
by this project is likely to have important clinical significance in the treatment of patients with
chondrosarcoma in that targeted miRNA may have potential to decrease chondrosarcoma cell
invasion and metastasis.
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 14
PATIENT REPORTED QUALITY OF LIFE AND FUNCTIONAL OUTCOMES AFTER SACRECTOMY
FOR CHORDOMA
Authors: Rishabh Phukan, BA, Tyler Herzog, BS, Kathryn Hess, Polina Osler, MBBS, Thomas
DeLaney, MD, Francis Hornicek, MD, Joseph Schwab, MD. In association with the Sacral Tumor
Study Group.
Institution: Massachusetts General Hospital
Introduction: En Bloc resection with negative margins is the current standard of care for
treatment of sacral chordoma. While surgical outcomes in patients with sacral tumor resection
have been studied previously in terms of patient survival, recurrence rates, and post-operative
complications, patient reported quality of life and functional outcomes are lacking. Previous
studies have focused on binary outcomes for bowel, bladder, and ambulatory function collected
retrospectively from chart reviews.
Methods: Quality of life and functional outcomes were collected in accordance with the
recommendations of The Sacral Tumor Study Group and include the following: PROMIS short
forms for Global Items (physical and mental subscores), Mobility (Lower extremity functional
score), Pain Intensity, Pain Interference, Anxiety, Depression, Sex Interest, Orgasm, Sex
Satisfaction, and Sexual Function Data was collected post-operatively from patients that had
undergone a sacral resection for treatment of chordoma. Patients were grouped by the level of
osteotomy as follows: Total Sacrectomy (N=6), S1 (N=8), S2 (N=10), S3 (N=5), and S4 (N=4).
Osteotomies which occurred between two vertebral levels were grouped with the more cephalad
level, i.e. half S1 was grouped with Total Sacrectomy, half S2 was grouped with S1, etc.
Osteotomy levels were determined by reviewing post-operative CT and MRI images.
Scores were calculated by converting PROMIS raw scores to T-Scores for analysis. Additionally,
the Modified Obstruction Defecation Score (MODS) and International Continence Society (ICS)
Voiding and Incontinence survey were used to evaluate bowel and bladder function respectively.
The data was analyzed on SigmaPlot 12 using One-Way ANOVA tests. A p value of less than
0.05 was considered statistically significant.
Results: A total of 33 patients (19 men and 14 women) were included in the analysis. Patients
had an average age of 55.8 Years (range: 22.55 – 77.25) and an average follow up of 40.7
months (range: 5.8 – 122.7) from surgery.
Our analysis showed a significant difference in quality of life between groups for PROMIS Global
Items-Physical subscore, Mobility, Pain Intensity, and Pain Interference.
PROMIS Global Items-Physical function was statistically different when comparing Total
Sacrectomy vs. S4, Total Sacrectomy vs. S2, S1 vs. S2, and S2 vs. S4,. PROMIS Mobility was
statistically different between Total Sacrectomy vs. S4, Total Sacrectomy vs. S2, and S1 vs. S4.
PROMIS pain intensity was different between Total Sacrectomy vs. S4, S1 vs. S4, S2 vs. S4, and
S3 vs. S4. PROMIS pain Interference was different between Total Sacrectomy vs. S4, S1 vs. S4,
and Total Sacrectomy vs. S2. These analyses were adequately powered (>0.8) with α=0.05.
Trends towards worse outcomes for higher osteotomy levels were observed in surveys for
PROMIS Global Items- Mental subscore, Sex Interest, Sex Satisfaction, Orgasm, MODS, and ICS
surveys. However, these analyses lacked statistical significance and were not adequately
powered. PROMIS anxiety and depression scores were statistically different between groups and
a trend towards significance was not observed.
Conclusions: Our findings are the first to use patient reported outcome scores to show the
effect of sacral tumor resection on quality of life and functional outcomes after sacrectomy for
chordoma. Physical function, mobility, and pain were all worse in patients who had higher
sacrectomies.
Our study lacked the power needed to show a difference between groups with regard to MODS,
ICS, Sex Interest, Sex Satisfaction, Global Items-Mental, and Orgasm although there was a trend
towards better function with lower sacrectomy.
Anxiety and depression scores were not different between groups and they approximated
scores seen with the normative data provided by the PROMIS website. Interestingly, we noted
that for certain subsets of patients with a lower level osteotomies, their quality of life
approaches, and at times exceeds, the average quality of life for the general population. This is
observed for Pain Interference, Pain Behavior, Global Item-Physical and Mental, Sex Interest, and
Sex Satisfaction.
In conclusion, our study provides data that can be used to help educate patients about their
expected quality of life and function after sacrectomy for chordoma. Patients with higher level
osteotomies had worse pain and function whereas some patients with lower sacrectomy
reported scores equal to and in some cases better than normative data.
SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 15
EFFECT OF SURGICAL MARGINS ON DISEASE-FREE SURVIVAL IN EXTREMITY, NONMETASTATIC, HIGH-GRADE OSTEOSARCOMA
Authors: Todd Bertrand, MD1; Alex Cruz, BS2; Odion Binitie, MD1; David Cheong, MD1; G.
Douglas Letson, MD1
Institutions: 1H. Lee Moffitt Cancer Center & Research Institute; 2University of South Florida
School of Medicine, Tampa, Florida
Background: Long-term (5-year) survival for all patients with osteosarcoma using current
treatment strategies is between 60-70%. In patients who present with non-metastatic, highgrade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over
amputation to preserve limb function and quality of life. However in the context of limb
salvage surgery in this patient cohort, the relationship between surgical margin and event-free
survival is unclear.
Questions/Purpose: We asked: (1) What is the effect of surgical margin on local recurrence?
(2) What is the effect of surgical margin on the development of metastatic disease?
Methods: With IRB approval, we retrospectively reviewed 241 patients treated at our institution
from 1999-2011. Exclusion criteria included non-extremity locations, metastatic disease at
initial presentation, low- or intermediate-grade osteosarcoma, treatment regimens that did not
follow neoadjuvant chemotherapy followed by local surgical control, incomplete medical
records, and any part of treatment performed outside of Moffitt Cancer Center or All Children’s
Hospital. 51 patients were included in the final analysis. Margin status was defined as 1)
Microscopically positive, 2) Negative ≤ 1mm, and 3) Negative > 1 mm. The average age was
22.3 years (range, 12 to 74 years) and the average follow-up was 3.22 years (range, 0.1 to 14.3
years).
Results: Margin status was positive in 9.8%, negative ≤ 1mm 25.5%, and negative > 1mm
64.7%. Overall survival at 3.84 years was 74.5% with a 5-year survival estimate of 0.69 (95%CI:
0.51, 0.81). Local recurrence rate was noted to be 13.7% at 3.42 years. There was worse local
recurrence-free probability at 3 years with positive margins (0.38, 95%CI: 0.01, 0.81) compared
to negative ≤ 1mm (0.83, 95%CI: 0.46, 0.95) and negative > 1mm (0.88, 95%CI: 0.66, 0.96), p =
0.027. Metastatic disease rate was 29.4% at 3.39 years with no difference in the probability of
developing metastatic disease between the three margin groups (p = 0.614).
Conclusions: In comparison to negative surgical margins, positive margins in patients with
extremity, non-metastatic, high-grade osteosarcoma showed a higher probability of local
recurrence but no significant difference in the probability of developing metastatic disease after
resection.
Level of Evidence: Level IV
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SESSION II: PRIMARY BONE TUMORS
Friday, October 10, 2014 | 1:00 PM – 2:30 PM
PAPER 16
TUMORAL TP53 AND/OR CDKN2A ALTERATIONS ARE NOT RELIABLE PROGNOSTIC
BIOMARKERS IN PATIENTS WITH LOCALIZED EWING SARCOMA: A REPORT FROM THE
CHILDREN’S ONCOLOGY GROUP
Authors: Daniel M. Lerman1,2, Michael J. Monument1,2, Elizabeth McIlvaine3, Xiao-qiong Liu4, Dali
Huang4, Laura Monovich5, Natalie Beeler5, Richard G. Gorlick6, Neyssa M. Marina7, Richard B.
Womer8, Julia A. Bridge4, Mark D. Krailo3, R. Lor Randall1,2, Stephen L. Lessnick1,2,9, for the
Children’s Oncology Group Ewing Sarcoma Biology Committee.
Institutions: 1Department of Orthopedics, University of Utah, Salt Lake City, UT, USA; 2Center
for Children’s Cancer Research, Huntsman Cancer Institute, University of Utah, Salt Lake City,
UT, USA; 3University of Southern California Keck School of Medicine, Los Angeles, CA, USA;
4
Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska
Medical Center, Omaha, NB, USA; 5Children’s Oncology Group Biopathology Center, The
Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; 6Department of
Pediatrics, Montefiore Medical Center, The Children's Hospital at Montefiore, Bronx, NY, USA;
7
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Stanford University, Palo
Alto, CA, USA; 8Division of Oncology, The Children's Hospital of Philadelphia, University of
Pennsylvania, Philadelphia, PA, USA; 9Division of Pediatric Hematology/Oncology and the
Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA
Purpose: A growing collection of retrospective studies have suggested that TP53 mutations
and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to
evaluate these variables in patients with localized disease treated prospectively on a single
Children’s Oncology Group protocol.
Patients and Methods: Of the 568 patients enrolled on Children’s Oncology Group protocol
AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to
allow for analysis of TP53 mutation status by DNA sequencing, and CDKN2A (9p21) locus copy
number by dual color fluorescent in situ hybridization.
Results: Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107
cases (11.2%) demonstrated homozygous loss of the CDKN2A locus. Two cases were found to
have an alteration in both genes. There was no significant difference in event-free survival of
patients with TP53 mutations and/or CDKN2A loss compared to patients with normal
TP53/CDKN2A gene status, as demonstrated by an insignificant relative hazard ratio of 1.26
[95% CI: 0.55 to 2.90].
Conclusion
Although previous retrospective studies suggest their significance, TP53 mutation and CDKN2A
loss are not reliable prognostic biomarkers in localized Ewing sarcoma.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 17
THE TREATMENT OF DIAPHYSEAL FEMUR FRACTURES IN THE METASTATIC RENAL CELL
CARCINOMA
Authors: Chapman Cadell, Patrick P. Lin MD, Bryan S Moon MD, Justin E. Bird MD, Robert
Satcher, MD, Valerae O. Lewis, MD.
Institution: MD Anderson Cancer Center
Introduction: Metastatic renal cell carcinoma (mRCC) commonly metastasizes to bone. Because
of the aggressive nature of the disease and its notorious radioresistance, the treatment of focal
metastasis remains controversial and often location dependent. Periarticular lesions are often
resected and reconstructed with an endoprosthesis, however resection and reconstruction of
diaphyseal lesions can be more difficult. Other metastases in the location are often addressed
with intramedullary (IM Rod) fixation, however this type of fixation in renal cell carcinoma
remains debatable. The goal of surgery for metastatic disease is to provide stable and durable
fixation, thus allowing the patient to pursue the highest functional outcome available to them
for the remainder of their lives.
Purpose/Question: The question arises whether intramedullary rod fixation of the impending
or pathologic metastatic RCC femur fracture, couple with curettage will provide adequate and
durable support for the remainder of the patient’s lifetime.
Methods: We performed IRB approved retrospective review of RCC patients that underwent
intramedullary rod fixation of diaphyseal femur or impending femur fractures from 2000 2010. 56 patients and 61 cases were identified. Medical records, pathology reports, operative
reports, radiographs and radiation records were reviewed. Patient demographics, use of intraoperative adjuvants, curettage, radiation, extra-osseous metastases, lesion progression,
revision of hardware, and perioperative complications were analysed.
Results: A total of 56 patients with 61 procedures were identified. Age ranged from 25 - 78
years old with the median of 57. Fourteen (25%) patients were female, 42 (75%) were male.
87.5% of these patients had metastases elsewhere in the body aside from the diaphyseal lesions
in question. The median OS time was 6.8 months (95% CI: 3.7, 11.6). The median follow-up
time for the censored observations was 22.0 months (range: 4.8 – 56.3 months). At last followup 49 (87.5%) patients had died of their disease. Forty six patients (82%) underwent intraoperative curettage and 21 patients (37%) underwent high speed burring of the lesion prior to
IM rod. Argon bean was used in 14 patients (25%) and cement augmentation was used in 41
patients (73.21%). Nine (16.07%) patients had pre-operative radiation and 26 (46.43%) patients
had post-radiation therapy. 10 patients (17.86%) had progression of the diaphyseal lesion but
only 12.5% of patients required revision. There was a statistically significant association
between progression and revision (p-value = 0.0149), 60% of patients received revision of
hardware in the group of patients who had progression compared to only 13% in the group of
patients who did not have progression. The associations between hardware revision and the
following variables were not significant: fracture, use of pre-operative radiation, curettage, high
speed burr, argon beam. The patients who receive post-operative radiation had higher rate of
hardware revision compared to the patients who did not receive post-operative radiation (23.1%
vs. 3.3%, p-value=0.0414).
Conclusion: The management of a diaphyseal impending or pathologic mRCC fracture with an
intramedullary rod is provides stable and durable fracture fixation for the patient with
metastatic renal cell carcinoma. The surgery is easier than the alternatives, and more
importantly, the vast majority of the time, it lasts through the duration of the patient’s life.
Instances of failure represented by a need for revision were relatively few.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 18
PREDICTORS OF REOPERATIONS AND COMPLICATIONS AFTER OPERATIVE TREATMENT
FOR METASTATIC FEMUR FRACTURES
Authors: Stein Janssen, MD*, Joost Kortlever, BSc*, John Ready, MD^, Kevin Raskin, MD*, Marco
Ferrone, MD^, Francis Hornicek, MD, PhD*, Joseph Schwab, MD MSc*
Institutions: *Massachusetts General Hospital, ^Brigham and Women’s Hospital,
Objective: We aim to assess which clinical- and treatment factors are associated with (1)
reoperations and (2) systemic complications in 30 days after operative treatment of metastatic
fractures of the femur.
Methods: After approval of this retrospective study by our institutional review board we used
diagnostic and procedure codes to identify patients with a metastatic fracture of the femur. We
included all patients above 18 years of age who were treated with intramedullary nailing,
endoprosthetic reconstruction, plate-screw fixation or a dynamic hip screw for a pathological or
impending fracture of the femur in two tertiary care referral hospitals between 1995 and 2014.
Exclusion criteria were: revision procedures of the femur, concomitant acetabular lesions
requiring acetabular reconstruction, condylar and supracondylar fractures.
Outcome measurements were: (1) any reoperation, and (2) systemic complications within 30
days after operative treatment. Explanatory variables were age, sex, side, type of fracture
(pathological or impending), anatomical location of the fracture, body mass index, Charlson
Comorbidity Index, type of operation, reaming and the use of cement.
We used a Cox proportional-hazards analysis to assess the association between explanatory
variables and reoperation. The association between explanatory variables and 30 day systemic
complications was assessed using the Fisher’s exact test for categorical explanatory variables
and the T-test for continuously distributed explanatory variables. Explanatory variables with a pvalue <0.20 will be included in a multivariate logistic regression analysis to assess
independence.
We included 659 patients, 48 had bilateral metastatic femur fractures requiring operative
treatment, totaling 707 cases. Among the 707 cases, 282 (40%) were men, mean age was 62
years (standard deviation [SD] 13 years). There were 333 (47%) pathological and 374 (53%)
impending fractures. Origin of most common primary tumors was: breast (29%), lung (19%),
myeloma (15%), kidney (7%) and prostate (6%). Two hundred and ten (30%) metastatic fractures
were located in the head/neck region, 196 (28%) intertrochanteric, 134 (19%) subtrochanteric
and 166 (23%) diaphyseal. Mean body mass index was 27 (SD 5.6), mean Charlson Comorbidity
Index 8.6 (SD 2.3). Median follow-up was 127 days (interquartile range 37 – 403, range 0 –
4266 days).
Results: We found 51 (7.2%) reoperations, primary reasons for reoperation were: deep infection
(14), implant fracture (12), peri-implant fracture or loosening (8), painful or massive recurrence
(7), hematoma (3), dislocation (2), painful nonunion (2), secondary arthritic changes (2), and
bursitis (1). Thirty-seven cases required implant replacement or additional fixation. There were
66 (9.2%) patients with 70 systemic complications; pneumonia (27), pulmonary embolism (20),
sepsis (11), myocard infarct (8) and fat/cement embolism (4).
As compared with patients who had an impending fracture, patients with a pathological fracture
had an increased risk of reoperation (hazard ratio 1.8; 95% confidence interval [CI] 1.05 – 3.2).
Patients who had plate-screw fixation had an increased risk of reoperation as compared to the
Disclosure information may be found on pages 51-60.
other operations (hazard ratio 4.8; 95% CI 2.3 – 10). Patients who had cementation during the
operation had an increased risk of reoperation as compared to patients who did not have
cementation (hazard ratio 1.9; 95% CI 1.1 – 3.3). Multivariate cox proportional-hazard analysis
demonstrated that plate-screw fixation as compared to the other operations (hazard ratio 4.2;
95% CI 1.7 – 10.3) was the only explanatory variable independently associated with reoperation.
A higher Charlson Comorbidity Index was the only explanatory variable associated with 30 day
systemic complications (p = 0.01). Multivariable logistic regression demonstrated that Charlson
Comorbidity Index was independently associated with 30 day systemic complications (Odds
ratio 1.1; 95% CI 1.0 – 1.3).
Discussion: Pathological fracture, plate-screw fixation and the use of cement were associated
with an increased risk of reoperation in univariate analysis. Plate-screw fixation was the only
variable independently associated with an increased risk of reoperation in multivariate analysis.
Charlson Comorbidity Index was the only variable associated with an increased risk of systemic
complications in both univariate and multivariate analysis. The reoperation (7.2%) and systemic
complication (9.2%) rates are similar to those reported in literature. Knowledge of risk factors
associated with reoperations and systemic complications can aid surgical decision making and
help inform the patient.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 19
TARGETING SKELETAL METASTASES USING HPMA COPOLYMER NANOPARTICLE DELIVERY
AND RETENTION
John Healey1, Alexander Christ2, Courtney Haviland3, Chloe Horowitz1, Steven Goldring2, Meera
Hameed1, Nicola Fabbri1, Zhanhua Jia4, David Wang4, Ed Purdue2
(1) Memorial Sloan Kettering Cancer Center, (2) Hospital for Special Surgery, (3) Weill Medical
College of Cornell University, New York, NY, (4) University of Nebraska Medical Center, Omaha,
NE
Background/Purpose: The goal for treating carcinoma-derived skeletal metastasis is to
develop a targeted drug delivery system that avoids the systemic and local toxicity of
chemotherapy and radiotherapy.
Solid tumors preferentially take up and retain nanoparticles via the Enhanced Permeability and
Retention (EPR) effect. The nanoparticles are then retained by myeloid cells via sequestration
into lysosomal compartments in a process termed ELVIS (Extravasation through Leaky
Vasculature and subsequent Inflammatory cell-mediated Sequestration).
Myeloid populations play a critical role in the local control of tumor cell growth and survival.
Macrophages function along a spectrum from classically-activated (M1) macrophages to
alternatively-activated (M2) macrophages. M1 macrophages function as antigen-presenting
cells that enhance immune responses, whereas M2 macrophages promote angiogenesis, wound
healing, and repair. In the tumor microenvironment, M1 cells are immunostimulatory, inducing
an anti-tumor response, whereas M2 cells exhibit immunosuppressant activity, conversely
supporting tumor growth and metastasis. NF-kB may influence macrophage function in solid
tumors. However, the importance of NF-kB signaling in driving cell activity in nearly all cell
types limits the safety of its effective systemic inhibition, necessitating the development of a
tumor-tropic drug carrier.
The goals of this study were to (1) confirm the presence of tumor-associated macrophages
(TAMs) in a clinical series of metastatic breast cancer specimens, (2) develop a model for
carcinoma metastatic to bone, (3) establish that HPMA localizes to the tumor site, and (4)
harvest TAMs to confirm uptake of HPMA into the macrophages and analyze the cells for
changes in gene expression.
Methods: Under an IRB-approved protocol, paraffin-embedded samples of non-irradiated
metastatic bone lesions from 40 breast cancer patients were histologically reexamined for
macrophage infiltration using immunohistochemistry with anti-CD68, a known pan-macrophage
glycoprotein. A bone pathology specialist confirmed the findings in all cases.
MDA-MB-231 human breast carcinoma cells were injected into the right tibial plateau of Balb/c
nude mice (5x104 cells/injection) with control injections of an equal volume of PBS into the left
tibial plateau. Weekly radiographs were then performed to detect evidence of tumor. Once
tumor growth was confirmed, HPMA-copolymer coupled to IR Dye and Alexa-Fluor was
administered via retro-orbital injection. In vivo infrared imaging was subsequently performed at
3, 24, and 48 hours post-injection.
Dose dependence of an NF-kappa-B inhibitor BMS-345541 on tumor cells and bone marrow
macrophages was analyzed by RT-PCR and flow cytometry. NOS2 and ARG1, molecular
indicators of M1 and M2 differentiation, respectively, were measured.
Results:
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We found substantial macrophage presence in all samples with a regional distribution in 10-50%
of fields. CD68+ cells were widespread in breast cancer bone metastases.
Tumors grew in 13 of 22 mice and were detectable radiographically between 6-12 weeks.
HPMA-copolymer localization to all tumors was confirmed via infrared imaging with increased IR
signal at 24 and 48 hours relative to the contralateral leg.
Next, HPMA-copolymer deposition within the tumor bed was confirmed with confocal
microscopy.
The remaining tumors were used for molecular biology experiments. Tumor cells were
recultured, then labeled using magnetic beads to separate TAMs from other cells. Other cells
were used in real-time PCR to observe activated macrophage gene expression profiles. Dose
dependence of an NF-kappa-B inhibitor on tumor cells and bone marrow macrophages was
analyzed by RT-PCR and flow cytometry. The NFkB inhibitor BMS-345541 altered gene
expression in bone marrow macrophages consistent with M1 polarization.
Conclusion: Breast cancer metastases in bone have a substantial macrophage presence with
CD68+ cells in all samples, distributed in 10-50% of fields. This confirms the potential for
clinically targeting tumor macrophages. Our metastatic carcinoma mouse model demonstrated
HPMA-copolymer localization to these tumors in vivo. This model can be used for targeted drug
delivery to metastatic cancer in bone, as well alter the balance of TAMs to promote or prevent
tumor growth.
Funding Sources: NCI Summer Fellowship Training Grant, Center for Molecular Imaging and
Nanotechnology Grant # CMINT 23, Pearlman Cancer Research Fund
Disclosure information may be found on pages 51-60.
SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 20
DOES RADIATION THERAPY AFFECT SURVIVAL AND FUNCTIONAL OUTCOMES OF NONHODGKIN LYMPHOMA OF BONE?
Authors: Ishaq Ibrahim, BS, Bryan D Haughom, MD, Yale A Fillingham, MD, Steven Gitelis, MD
Institution: Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL
Introduction: Non-Hodgkin Lymphoma (NHL) of bone is a rare malignancy accounting for less
than 7% of all bone tumors. Excellent treatment outcomes have limited surgical management to
biopsy and the treatment of complications. With recent studies reporting excellent survival with
medical treatment (chemotherapy and Rituximab), the role of radiation has come into question.
We sought to evaluate the survival and functional outcomes, as well as complications of
radiation treatment in a large cohort of patients with NHL of bone.
Methods: A retrospective analysis of all biopsy proven NHL of bone diagnosed at our
institution between 1985 and 2013 was undertaken. Both primary and secondary NHL of bone
were included in our analysis. Musculoskeletal Tumor Society (MSTS) scores were calculated for
all patients with appendicular tumors who were alive at the time of analysis. Scores were
compared using T-tests. Overall survival (OS) was estimated using the Kaplan-Meier method,
and a log-rank test was used to compare survival between patients receiving combined-modality
therapy (chemotherapy and radiation) and those treated without radiation. The rate of fracture
was compared between treatment groups using a Fisher's exact test.
Results: The study population included 70 patients (42 males, 28 females), with 39 (55.7%)
carrying a diagnosis of primary lymphoma of bone (PLB). Average follow up was 59.6±49.5
months. Mean age was 53.5±18.0 years. Sixty-two patients (88.6%) presented with
appendicular tumors (39 lower extremity) and 8 with axial lesions (6 spine). The femur was the
most frequent site of disease (21 patients, 30.0%) and Diffuse Large B-Cell Lymphoma (DLBCL)
was the most common histological subtype observed (57 cases; 81.4%). Radiation was
employed in 24 patients (34.3%; mean dose 39.4±6 Gy). There were no differences (p>0.05)
observed between the radiated and non-radiated cohorts with respect to age, sex, site of cancer
(weight-bearing vs. non-weight-bearing bone), lymphoma subtype (DLBCL vs. indolent
lymphoma) and localized vs. advanced disease.
Survival:
Overall Survival was 96% at 5 years and 75% at 10 years. No difference in survival was observed
between patients treated with combined-modality therapy and patients treated without radiation
(94% vs. 97% at 5 years, and 71% vs. 80% at 10 years; p=0.321). Overall survival for patients
with primary lymphoma was 97% at 5 years and 86% at 10 years, and OS for secondary
lymphomas was 96% and 69% at 5 and 10 years respectively (p=0.228).
Complications:
Twenty-five patients (35.7%) initially presented with orthopaedic complications—21 pathological
fractures, 2 cases of spinal cord compression, and 2 cases of femoral head osteonecrosis. Eight
(38.1%) of these pathological fractures underwent surgical stabilization, one of which required a
revision surgery for disease progression. Five of the pathological fractures (23.8%) were
radiated including one patient who also underwent surgery. Of the five radiated fractures, 4
(80%) experienced abnormal healing including delayed union (1), malunion (1), and nonunion
(2). The remaining 8 fractures (38%) in this group were treated nonoperatively and healed
uneventfully.
Nineteen patients presented without fracture and were treated with radiation. Five patients
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(26.3%) in this group sustained fractures after treatment, while none occurred in the nonradiated group (p=0.004). Abnormal healing was observed in each of these fractures including
malunion (1), delayed union (1), and nonunion (3) requiring surgical intervention.
Function:
MSTS scores were obtained on 42 patients (response rate: 82.4%) with appendicular tumors at
an average follow up of 52.8±46.7 months. Overall function was excellent with an average MSTS
score of 25.9±4.8 (86.3%). Patients experiencing radiation-related complications reported
poorer outcomes (n=7; average: 18.6±5.53; 61.9%) compared to those without complications
(n=35; average 27.3±3.0, 91.1%, p=0.008). Functional outcomes were no different in those
patients with upper extremity lesions (n=16; average 27.7±3.3, 92.3%) and lower extremity
lesions (n=26; average 24.8±5.3, 82.6%; p=0.082).
Conclusion: Consistent with prior literature, our data confirms that the modern treatment of
NHL of bone has resulted in excellent survival outcomes. Prior studies examining the role of
radiation therapy in the treatment of this disease have yielded mixed results. Our data
demonstrates no survival benefit to radiation therapy and a significant increase in the rate of
fracture and bony complications. Furthermore we demonstrate the first functional evaluation of
treated NHL of bone, which demonstrates excellent functional scores in the absence of bony
complications further calling into question the role of radiation therapy.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 21
PARATHYROID HORMONE TRANSIENTLY PROTECTS BONE FROM RADIOTHERAPY-INDUCED
DAMAGE
Authors: M.E. Oest1, Kenneth A. Mann1, Nicholas Zimmerman1, Nicholas Allen1, Timothy A. Damron1
Institutions: 1Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, NY
Introduction: Late-onset bone fragility fractures are a devastating complication following
radiotherapy for soft tissue sarcoma or metastatic disease. Clinical retrievals from these patients are
characterized by loss of trabecular bone, diminished bone cellularity, and loss of mechanical
strength. There are currently no preventative clinical strategies or treatments to restore bone integrity
following radiation-associated damage. The goal of this study was to assess the potential of
parathyroid hormone fragment 1-34, an anabolic agent, to maintain bone structure and strength
following focal irradiation in a mouse model.
Methods: Female BALB/CJ mice aged twelve weeks were anesthetized and exposed to unilateral
hindlimb irradiation (RTx) delivered as four consecutive daily fractions of 5 Gy each (4x5Gy, n=7
mice/group/time point). The non-irradiated hindlimb served as a 0Gy control. Beginning the first day
of irradiation, mice were given injections of either parathyroid hormone (1-34) (PTH, 40 ug/kg) or
vehicle (VEH) five days per week for eight weeks. Mice were euthanized for femur collection at 0, 1, 2,
4, 8, and 12 weeks post-RTx. Femurs were micro-CT scanned at a 12 um voxel resolution.
Quantitative 3D morphometric and mineral density analysis was done for four volumes of interest: the
distal 5mm of the femur, a 1mm thick section of the mid-diaphyseal cortex, a 0.4mm thick volume of
epiphyseal trabecular bone, and a 0.75mm thick volume of metaphyseal trabecular bone. Outcome
measures included: bone volume, bone volume fraction (BV/TV), bone mineral density, bone mineral
content, trabecular number, trabecular thickness, trabecular spacing, and connectivity. Following
micro-CT imaging, femurs were subjected to axial compression testing. Mechanical testing outcome
measures included ultimate load, stiffness, and work to ultimate load.
Results: Trabecular connectivity was decreased by irradiation and not restored with PTH treatment.
Similarly, the RTx-induced increase in trabecular bone mineral density was not reduced by PTH
augmentation. Metaphyseal BV/TV decreased in RTx samples at 8 and 12 weeks. PTH protected
metaphyseal trabecular BV/TV against this decrease through week 8, but not at week 12. Epiphyseal
trabecular BV/TV did not decrease following RTx, but was consistently increased by PTH treatment.
Both PTH and RTx treatments increased trabecular thickness. Trabecular spacing was increased by
RTx and decreased by PTH therapy.
Bone volume in the distal femur and mid-diaphyseal cortex was increased by PTH treatment. RTx also
increased bone volume over controls in the distal femur, but transiently decreased BV in the mid-shaft
cortex at 8 weeks. Distal femur bone mineral density was increased by RTx at eight and twelve weeks.
PTH augmentation of RTx samples did not attenuate the 12-week RTx-induced increase in distal
femur BMD.
Irradiation induced a consistent biphasic response in ultimate load, stiffness, and work to ultimate
load. These parameters were increased over controls at early time points, but decreased at 8 and 12
weeks. Ultimate load was increased in RTx samples compared to controls at one week, but by eight
weeks irradiated samples were less strong than controls. PTH treatment increased ultimate load
above control and irradiated values at all time points. Stiffness was significantly decreased in both
RTx groups by week 12. Work to ultimate load was increased by PTH treatment from 0-8 weeks, but
decreased in RTx-PTH femurs at week 12. Radiation induced an early transient increase in ultimate
load, but decrease by 12 weeks.
Discussion: PTH treatment conferred some transient protection against radiation-induced changes in
bone morphology. By week 12 however, PTH-RTx samples were generally similar to VEH-RTx samples.
The transient benefit of PTH therapy was similarly demonstrated in mechanical strength, where PTHRTx samples demonstrated parity with VEH-RTx by week 12. These data suggest that the benefits of
PTH therapy may persist only through the duration of treatment.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 22
THE ACCURACY AND CLINICAL UTILITY OF INTRAOPERATIVE FROZEN SECTION ANALYSIS
IN OPEN BIOPSY OF BONE
Authors: Matthew T Wallace MD, Micheal Deavers MD, Patrick P Lin MD, Bryan S Moon MD,
Justin E. Bird MD, Robert Satcher, MD, Valerae O. Lewis, MD
Introduction: Open biopsy of bone is the gold standard for the diagnosis of skeletal lesions.
Open biopsy may be performed for several reasons, such as prior nondiagnostic needle biopsy,
confirmation of diagnosis prior to planned surgical intervention, or other institutional and
logistical reasons. Intraoperative pathology consultation with frozen section analysis is
commonly performed at the time of open biopsy to confirm adequacy of lesional tissue and
guide intraoperative decision-making, but frozen section interpretation can be limited by the
technical considerations of freezing certain tissues and the inability to perform specialized
staining, flow cytometry, and other molecular testing.
Purpose: The goal of this study was to determine the overall accuracy and clinical utility of
intraoperative frozen section analysis in the setting of open bone biopsy.
Methods: We performed a retrospective review of 467 patients that underwent open biopsy of
osseous lesions between 1997 and 2014. Pathology reports, operative and clinical notes, and
prebiopsy imaging were assessed to determine accuracy rates of frozen section analysis.
Results were classified as “accurate” when frozen section and permanent section results were
concordant, “equivocal positive” when frozen section was only able to provide a partial
interpretation, such as differentiating nontumoral or benign disease versus malignancy, or
sarcoma versus other malignancy, “equivocal negative” when frozen section results were
inconclusive or deferred to permanent section, and “incorrect” when frozen section and
permanent sections were discordant. Pearson Chi-Square test was performed to compare
accuracy rates based on the presence of tumor soft tissue extension, a history of prior biopsy,
lesional consistency (sclerotic, mineralized, solid, or cystic), class of disease (benign,
metastatic, sarcoma, hematologic, and non-tumoral), and anatomic location.
Results: The overall diagnostic yield of open bone biopsy was 94.65%. Frozen section analysis
was accurate in 47.97%, equivocal positive in 22.48%, equivocal negative in 25.91%, and
incorrect in 3.64% of cases. Prior biopsy (p value < 0.001) and class of disease (p value <
0.001) were found to have statistically significant effects on the accuracy of frozen section
analysis. Among the most common nondiagnostic and incorrect biopsies, lymphoma of bone
and primary sarcoma of bone were among the most common diagnoses.
Conclusion: Frozen section analysis was accurate in less than half of biopsy cases. The
additional information provided by equivocal positive results suggests that frozen section
analysis proved helpful for intraoperative decision-making (overall clinical utility) in 70.45% of
cases. The presence of a prior biopsy was significantly correlated with the accuracy of frozen
section, suggesting that a prior nondiagnostic needle biopsy does not necessarily indicate
sampling error, and can reflect the complexity of a case. Type of disease, particularly
hematologic malignancies and primary bone sarcomas, had an adverse effect on accuracy.
Accuracy rates based on the presence of soft tissue extension, the consistency of the lesion,
and the anatomic location of the lesion were not found to be statistically significant. These
results support the view that the diagnosis of osseous lesions is a complex undertaking, and
must take into account several clinical, radiographic, and pathologic factors. A blind biopsy in
the operative setting can therefore be subject to considerable error, and prebiopsy workup
should be completed to the furthest extent possible to minimize the risk of improper surgical
intervention.
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SESSION III: METASTATIC DISEASE, LYMPHOMA, AND MULTIPLE MYELOMA
Saturday, October 11, 2014 | 7:30 AM – 9:10 AM
PAPER 23
INFLUENCE OF MESENCHYMAL STROMAL CELLS ON PULMONARY METASTASIS AND LOCAL
RECURRENCE IN A MURINE MODEL OF MINIMAL RESIDUAL DISEASE FOLLOWING
AMPUTATION OF PRIMARY OSTEOSARCOMA
Authors: Nicole Ehrhart, DVM, MS, Megan Aanstoos-Ewan, MS, Ruth Rose, DVM, Dan Regan,
DVM
Institution: Colorado State University, Fort Collins, CO, USA.
Introduction: Mesenchymal stromal cells (MSCs) have been shown to improve bone integration
and healing in several preclinical studies and have therapeutic potential in limb salvage
following massive bone loss due to tumor resection. However, MSCs have also been shown to
promote primary and pulmonary metastatic tumor growth when injected in the presence of
gross tumor or when co-injected with tumor cells in rodent models. While these results raise
concerns about the safety of using MSCs in sarcoma patients, MSCs are unlikely to be utilized in
a clinical setting when gross tumor is present.
Osteosarcoma (OSA) is the most common primary bone sarcoma. Surgical removal of the
primary tumor involves amputation or limb salvage, with the latter method requiring
reconstruction and bone healing. The objective of this study was to develop a murine model of
osteosarcoma that mimics OSA in the post-surgical setting to determine whether the
administration of adipose-derived MSCs in a minimal residual disease setting would promote
either pulmonary metastatic OSA progression or local disease recurrence. We hypothesized that
local (surgical site) or IV injection of MSCs would not influence progression of pulmonary
metastatic burden or local disease recurrence in a minimal residual disease setting.
Methods: A syngeneic model of OSA was developed to mimic the natural disease progression of
osteosarcoma wherein an orthotopic luciferase-expressing primary OSA tumor was established
in the tibia of C3H mice. When the tumor-bearing mice undergo coxofemoral amputation at 14
days post-tumor cell inoculation, no gross evidence of metastasis exists; however, 100% of mice
will develop metastatic disease within 15 days following amputation. A secondary model was
also developed in which, instead of coxofemoral amputation, a femorotibial amputation was
performed in order to develop a model of consistent local tumor recurrence. In this model all
gross tumor is removed, however, histologocal evaluation of the resected limbs indicates
remaining microscopic tumor at the surgical margin and in 90% of mice operated in this
fashion, local recurrence was present within 20 days following femorotibial amputation. Using
these two experimental models, 126 C3H mice had 1x106 luciferase-transfected DLM8-M1
osteosarcoma cells injected into the proximal tibia. Primary tumor formation was confirmed in
vivo using the PerkinElmer In Vivo Imaging System (IVIS). Fourteen days after tumor
inoculation, 86 mice underwent a coxofemoral amputation to remove the primary tumor with
wide margins and were placed in the metastasis study group. Forty mice underwent a
femorotibial amputation and were placed in the local recurrence study group. Following
assignment into either the local recurrence study or the metastasis study, mice were
randomized to receive adipose-derived C3H MSCs injected either at the site of amputation,
systemically through the tail vein, or no MSCs (controls) . Development and progression of
pulmonary metastases was monitored using IVIS imaging. Development and progression of
local recurrence was monitored by IVIS imaging, daily examination and caliper measurements at
the amputation site. Mice were sacrificed 24 days following tumor inoculation. At necropsy,
lungs and amputation sites were collected, imaged, and then examined histologically. The total
number of pulmonary metastatic nodules per animal were counted. Area of the total lung tissue
per section was measured and sections combined using commercial digital imaging software.
Percentage of metastatic area relative to total lung area was calculated. Time to tumor
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recurrence (days) and size of recurrent tumor was calculated using RECIST criteria. Data were
expressed in mean ± SD. A Kruskal-Wallis test was utilized for analysis of metastatic number,
metastatic area and tumor volume and a Fisher’s Exact test was used to compare presence or
absence of disease. Significance was set at p <0.05..
Results:
Metastasis Study Group: The median number of metastatic nodules among animals treated with
intravenous MSCs was 7.5 whereas the median number of metastatic nodules among animals
treated with local delivery of MSCs or no MSCs was 1.5 and 1.5 respectively. No statistical
difference was noted between groups (p=0.44) or between pairwise comparisons however.
Likewise, with respect to the percentage of metastatic area of lung to total area, no significant
difference was noted (p=0.13)
Local Recurrence Study Group: No significant difference was seen between groups with respect
to time to tumor recurrence or size of recurrent tumor in any group.
Conclusions: In this model of OSA designed to mimic a post-operative minimal residual disease
setting, the local administration of MSCs did not promote metastatic disease burden or local
tumor recurrence. Intravenous administration of MSCs increased the relative number of gross
metastatic nodules in mice as compared to controls or locally delivered MSCs but the increase
was not statistically significant.
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SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 24
DOES OBESITY EFFECT SOFT-TISSUE SARCOMA OUTCOMES?
Authors: John Harris MD, Shawn Morrell MD, Richard Nicholas MD, Corey Montgomery MD, MS
Institution: University of Arkansas Medical Sciences, Department of Orthopaedic Surgery, Little
Rock, Arkansas
Introduction: The obesity epidemic has far reaching consequences and is widely recognized as
not only a medical issue, but a complicating influence in the management of a variety of
medical problems. This has been particularly problematic in the South where the problem of
obesity has the greatest effect. Using BMI and other descriptors of obesity, there is evidence
implicating obesity as an overall negative health risk factor. In the area of cancer research,
obesity has been linked not only to increased risk of multiple cancer types but also to
subsequent complications in the management of these malignancies. It could also be a
potential barrier in the initial diagnosis of malignancies, since because body habitus could limit
early detection. This may be especially apparent in the area of soft tissue sarcomas, where
diagnosis is usually heralded by the observation of a new mass on a patient’s body.
Given the high incidence of obesity in our patient population, it would therefore be valuable to
examine the characteristics of malignant soft tissue sarcomas in this patient population. In fact,
we propose that an enlarged body habitus associated with obesity could limit the ability of early
recognition. Given this, we hypothesized that increasing BMI limits the ability to detect softtissue sarcomas at smaller sizes. This increased time for tumor growth prior to detection
increases the potential for more extensive operations needed for surgical removal with possible
associated wound healing related problems, metastatic spread and overall decreased survival.
Material and Methods: One-hundred and forty-three patients with soft-tissue sarcomas of the
extremities were retrospectively evaluated over a ten-year time period. Patients were divided
into five cohorts based on the World Health Organization BMI obesity grouping to include
individuals with normal BMIs (<24.9), overweight BMIs (<29.9), and those with Class I (<34.9), II
(<39.9) and III (>40) obesity BMIs. Demographic, staging, surgical and patient outcome data
were collected. A series of univariate and logistic regression analyses were performed to
evaluate the data. In some instances, patients with a BMI >30 were compared with patients with
a BMI <30 for statistical purposes. Hand/forearm soft-tissue sarcomas were excluded from the
comparative analysis, since body habitus in these locations does not routinely obscure
detection.
Results: There were 85 five patients in the BMI <30 category and 54 patients in >30 category.
Sarcomas were most commonly found in the thigh followed by the leg/foot. Excluding hand and
forearm soft-tissue sarcomas, patients with a BMI >30 had significantly larger sarcomas
(p=0.001) and were associated with significantly more wound complications (p=0.01) following
surgical excision. A BMI >30 did not correlate with whether or not the excision was planned or
unplanned. However, in the case of high-grade sarcomas, BMI >30 was significantly correlated a
higher stage at diagnosis (p=0.01) and worse overall survival (p<0.05).
Conclusion: The ramifications of obesity continue to be discovered. Our findings suggest that
obesity not only negatively effects surgical management of soft-tissue sarcomas but also
significantly decreased survival in this patient population. There is a need to be aware of the
BMI of soft tissue sarcoma patients. Further evaluation is required to ascertain whether BMI
should be considered is a critical risk factor before and after surgical excision.
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SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 25
OBESITY DOES NOT AFFECT SURVIVAL OUTCOMES IN EXTREMITY SOFT TISSUE SARCOMA
Authors: Vignesh K. Alamanda BS, David C. Moore MD, Yanna Song MS, Herbert S. Schwartz
MD, Ginger E. Holt MD
Institution: Vanderbilt Medical Center
Background: Obesity is a growing epidemic and has been associated with an increased
frequency of complications after a variety of surgical procedures. Studies have also have shown
adipose tissue to promote a microenvironment favorable for tumor growth. Additionally, the
relationship between obesity and prognosis of soft tissue sarcomas (STS) has yet to be
evaluated. Therefore, we sought to assess if (1) obesity affects survival outcomes (local
recurrence, distant metastasis and death due to disease) in patients with extremity STS; and (2)
whether obesity affected wound healing and other surgical complications after treatment.
Methods: A body mass index (BMI) of over 30 kg/m2 was used to define obesity. Querying our
prospective database between 2001 and 2008, we identified 397 patients for the study; 154
were obese and 243 were not obese. Mean followup was 4.5yrs(SD: 3.1yrs) in the obese group
and 3.9yrs(SD: 3.2yrs) in the non-obese group. Outcomes, including local recurrence, distant
metastasis, and overall survival, were analyzed after patients were stratified by BMI.
Multivariable survival models were used to identify independent predictors of survival
outcomes. Wilcoxon rank sum test was used to compare continuous variables.
Results: Obese patients had similar survival outcomes and wound complication rates when
compared with their non-obese counterparts. Obese patients were more likely to have lower
grade tumors (31% vs. 20%; p = 0.021) and additional comorbidities including diabetes mellitus
(26% vs. 7%; p < 0.001), hypertension (63% vs. 38%; p < 0.001), and smoking (49% vs. 37%; p =
0.027). Regression analysis confirmed that even after accounting for certain tumor
characteristics and comorbidities, obesity did not serve as an independent risk factor in
affecting survival outcomes.
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SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 26
MAGNETIC RESONANCE GUIDED HIGH INTENSITY FOCUSED ULTRASOUND: A NOVEL
NONINVASIVE TECHNIQUE TO TREAT SOFT TISSUE TUMORS OF THE EXTREMITY
Authors: Raffi S. Avedian MD*, Rachelle Bitton PhD, Garry Gold MD#, Kim Butts-Pauly PhD#,
Pejman Ghanouni MD/PhD#
Institutions: *Stanford University Deptartment of Orthopedic Surgery. #Stanford Univ
Department of Radiology
Introduction: Local control treatment modalities for soft tissue tumors such as radiation and
surgery are associated with morbidity which may include wound infections, scarring, nerve
injury, joint stiffness, and prolonged recovery. Over the last few decades there have been
relatively few improvements in surgical treatments for soft tissue tumors. Magnetic resonance
guided high intensity focused ultrasound (MRgHIFU) thermal ablation is a relatively new
noninvasive treatment modality that can ablate solid tumors while sparing surrounding normal
tissues (Figure 1). MRgHIFU is FDA approved for treating uterine fibroids and metastatic bone
disease and the purpose of our study is to adapt this technology to treat soft tissue tumors of
the extremity.
Background: MRgHIFU is based on the physical properties of sound. When propagating
through human tissue, the acoustic energy of the sonic pressure wave causes tissue shearing
on a microscopic level that leads to frictional heating. In most circumstances, ultrasound
travels through human tissues with very little energy deposition and no detectable rise in
temperature or other harmful effects. However, when multiple acoustic pressure waves
converge onto a designated focal point, sufficient energy is deposited into a focused volume to
cause heating and thermal necrosis of the tissue. Because heating only occurs where the
ultrasound waves converge, the surrounding tissue remains unaffected. When treating tumors
in a clinical setting, multiple treatment foci are targeted within the tumor in an overlapping
manner such that at the completion of therapy the sum of all the ablations results in complete
tumor thermal necrosis. MR thermometry is done in real time during the HIFU treatment and
allows direct visualization and temperature mapping of the target tissue (Figure 2). This
technology is a potentially a new noninvasive treatment modality for ablating soft tissue tumors
in the extremity. Research to understand its effectiveness and safety must be performed.
Purpose: The purpose of this study was to determine the feasibility of using MRgHIFU
technology to treat soft tissue tumors of the extremity and to report our experience using
MRgHIFU in 5 patients with desmoid tumors. We specifically asked: (1) can we use
commercially available MRgHIFU equipment to accurately ablate a predetermined target volume
within a human cadaver extremity? and (2) What are the preliminary results of MRgHIFU
treatment in human patients with desmoids tumors?
Methods: We used a commercially available HIFU system to perform thermal ablation of
simulated tumor volumes in four human cadaver extremities. The simulated tumor volumes
were created by percutaneously inserting plastic intravenous catheters in a predetermined
geometric pattern into the cadaver muscle. These catheters are visible on MR imaging and
define the boundary of the simulated tumor. We conducted the ablations using standard
settings of the MRgHIFU device which included a frequency range of 0.9MHz to 1.35MHz and
energy deposition of 800J-2900J per sonication. The goal of treatment was to ablate the
simulated tumor volume. Upon we then dissected each cadaver limb and measured the actual
area of tissue ablation and compared that to the intended area of ablation. Accuracy was
determined by measuring the location error according to the International Organization of
Standards (ISO). The location error is defined as the longest vertical distance between the
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predicted ablation plane and the farthest point of actual ablation. We examined each specimen
for complications such as skin burns and unintended nerve or vascular burns. After completion
of the cadaver studies we obtained approval from our institution's ethics committee to perform
MRgHIFU on 5 patients with desmoid tumors. Two patients had progressive disease in spite of
exhausting standard treatments, and 3 patients declined surgery, radiation, and systemic
treatment. All patients were extensively counseled and signed a comprehensive consent
document.
Results: The ablation accuracy for the four cadaver extremities was 5mm, 3mm, 8mm, and
8mm. There were no gross neurovascular structure burns. In a lower leg specimen where the
target volume was in the soleus muscle we noticed unanticipated burning along a thick portion
of the gastrocnemius aponeurosis. In all five patients the treated portion of the tumor, which
avidly enhanced with contrast prior to treatment did not enhance after treatment. Average
followoup was 12 months. There were no major complications. In one patient the tumor
completely resolved and the remaining 4 patients the tumors stopped growing or became
smaller (Figure 3). Overall function using the MSTS outcome score either improved or was
stable after completion of treatment.
Conclusion: MRgHIFU can be used to accurately ablate tumor volumes in the extremity. Initial
experience treating desmoid tumors is encouraging and warrants further investigation.
Figure 1 Schematic of a HIFU treatment of sarcoma located in the vastus medialis.
The yellow lines represent ultrasound waves that propogate through the thigh
without causing. At the focus the waves converge and cause heating of the target
tissue while the surrounding tissue are unharmed. The heat is sufficient to ablate a
volume approximately the size of a grain of rice. Multiple sonications are performed
until the desired volume of tissue is ablated.
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Figure 2. MR guided high-intensity focused ultrasound (HIFU) ablation in a cadaver lower leg. (A) Axial T1 MR
image of a human cadaver lower leg undergoing HIFU planning. The yellow cylinders represent planned areas of
sonication, in this case where the rice noodles were placed as fiducials. The blue hourglass represents the
trajectory of the ultrasound energy with the focus located at the waist. (B) Coronal T1 MR image. The yellow
circles represent the coronal view appearance of the same areas to be sonicated. (C) Coronal T1-weighted image of
the area treated (blue) by MR thermometry. (D) Tissue
specimen showing treated area.
A
B
C
Figure 3. Twelve year old boy who had (A) an enlarging desmoid tumor of his right buttock as seen on this T2 weighted MR
image. He had local recurrences after two operations including a left above knee ampuation. He had stable disease while
on chemotherapy but progessive disease when he stopped systemic treatment. He underwent two MRgHIFU treatments
with (B) T1 fat suppressed post contrast MRI showing necrosis of the tumor and (C) near complete resolution of the tumor
as seen on a 4 month followup T2 weigted MRI.
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SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 27
TRANSCUTANEOUS OXIMETRY CAN PREDICT WOUND HEALING IN PREOPERATIVELY
RADIATED SOFT TISSUE SARCOMA
Authors: Lukas M. Nystrom, MD, Benjamin J. Miller, MD
Institution: Investigation performed at the University of Iowa
Background: External beam radiation therapy is recommended in combination with surgical
resection to improve local control in the treatment of high-grade soft tissue sarcoma. Radiation
can be performed either preoperatively or postoperatively with equivalent local control1,2.
Advantages of preoperative radiation include smaller overall field size and dose which is
believed to result in improved function of the spared limb3. Furthermore, it may potentiate limb
salvage by allowing safe marginal resection along vital neurovascular structures1. Preoperative
treatment comes at the cost of increased wound complication rate when compared to postoperative therapy3. Currently surgical timing is recommended at 3-6 weeks post-radiation with
no particular data to guide the decision of optimal timing. A prior investigation has made a link
between a decreasing transcutaneous oxygen (TcO 2 ) level measured in the post-operative
period (Days 1-5) and wound healing4. However, as the wounds were tested in the postoperative period the study was limited with regard to the cause of the decreased TcO 2
(radiation, tumor factors or surgical resection technique). Our hypothesis is that anoxic tissue
from pre-operative radiation may contribute to surgical wound complications and that TcO 2
measurements made preoperatively can predict wounds at risk.
Materials and Methods: Ten consecutive patients with lower extremity sarcoma deemed
appropriate for preoperative radiation by a multidisciplinary sarcoma board were enrolled in the
study. TcO 2 measurements were obtained at five time points: prior to start of radiation, halfway
through radiation, at the completion of radiation, immediately preoperatively and two weeks
postoperatively. TcO 2 was measured at 5 locations around the operative field and on the
contralateral limb. Average time to surgery was 28.3 days. All patients were treated by the
same surgeon with a standard wound closure protocol. One patient required an immediate flap
for required resection of skin associated with a subcutaneous sarcoma. Wound complications
and healing outcomes were recorded out to 4 months post-operatively. Wound complications
were defined as major or minor. Major complications included the need for operative wound
management (irrigation and debridement, wound closure, skin graft or flap), readmission for IV
antibiotics, and need for dressing changes or wound packing for greater than 120 days after
the operation. Minor complications included aspiration of a seroma, need for oral antibiotics,
and need for dressing changes or wound packing for greater than 4 weeks.
Results: There were three major complications and one minor wound complication. Major
complications included one deep infection identified 6 weeks after surgery, one wound
radiation necrosis identified at 5 weeks after surgery and one hematoma requiring drainage two
months after surgery. The minor complication noted was in a patient who had prolonged
wound drainage greater than 6 weeks which eventually sealed at three months postoperatively.
This patient was treated with daily dressing changes but no operative intervention. The average
mean (mean of all five leads) TcO 2 measurement was 51.8 mmHg pre-radiation, 57.1 mmHg
mid-treatment, 53.3 mmHg post-treatment, 49.5 mmHg pre-operatively and 54.0 mmHg postoperatively. The mean low reading was 30.5 mmHg, 35.3 mmHg, 33.4 mmHg, 27.5 mmHg and
30.8 mmHg, respectively. Patients without complications had a mean preoperative TcO 2 of
53.8 mmHg compared to 42.9 mmHg in patients with complications (p=0.16). Patients without
complications had a low preoperative TcO2 of 33.4 mmHg compared to 18.7 mmHg in patients
with complications (p=0.09). No patients with a TcO2 of greater than 25 mm Hg on the
immediate preoperative measurement (0/3) had wound complications, while 57% (4/7) of
patients with TcO2 of less than 25 mm Hg did.
Disclosure information may be found on pages 51-60.
Conclusions: Our data indicate that a “rest period” of one month following EBRT offers no
predictable recovery in TcO 2 skin measurements. With regard to wound complications the
immediate preoperative measurement seems the most important in predicting wound
complications, with no patients with a minimal TcO 2 measurement greater than 25 mmHg
experiencing a wound complication. Transcutaneous oximetry represents a potential tool for
decisions regarding surgical timing or potentially other medical and surgical efforts to diminish
wound complications. However, given this small sample size more data is needed to further
assess the relationship.
Level of Evidence: Level II, diagnostic.
References
1. Dagan R, Indelicato DJ, McGee L, Morris CG, Kirwan JM, Knapik J, Reith J, Scarborough
MT, Gibbs CP, Marcus RB, Jr., Zlotecki RA. The significance of a marginal excision after
preoperative radiation therapy for soft tissue sarcoma of the extremity. Cancer 2012;11812:3199-207.
2. Trovik CS, Scanadinavian Sarcoma Group P. Local recurrence of soft tissue sarcoma. A
Scandinavian Sarcoma Group Project. Acta Orthop Scand Suppl 2001;72-300:1-31.
3. O'Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, Wunder J, Kandel R,
Goddard K, Sadura A, Pater J, Zee B. Preoperative versus postoperative radiotherapy in softtissue sarcoma of the limbs: a randomised trial. Lancet 2002;359-9325:2235-41.
4. Conlon KC, Sclafani L, DiResta GR, Brennan MF. Comparison of transcutaneous oximetry
and laser Doppler flowmetry as noninvasive predictors of wound healing after excision of
extremity soft-tissue sarcomas. Surgery 1994;115-3:335-40.
Disclosure information may be found on pages 51-60.
SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 28
MRI CAN BE USED TO RISK STRATIFY PATIENTS WITH EXTRA-ABDOMINAL DESMOID
FIBROMATOSIS
Authors: Firouzeh Kamali 1, 7, Wei-Lien Wang 2, Ashleigh Guadagnolo 3, Patricia S. Fox 4, Valerae
O. Lewis 5, Alexander J. Lazar 2, Anthony P. Conley 6, Mohammad Toliyat 1, 8, Harshad S. Ladha 1,
Brian P. Hobbs 4, Behrang Amini 1
Institutions: Departments of (1) Diagnostic Radiology, (2) Pathology, (3) Radiation Oncology,
(4) Biostatistics, (5) Orthopedic Oncology, and (6) Medical Oncology, The University of Texas
M.D. Anderson Cancer Center, Houston, TX; Departments of (7) Diagnostic Radiology and (8)
Internal Medicine, The University of Texas at Houston, Houston, TX.
Background: Extra-abdominal desmoid fibromatosis is benign, locally aggressive neoplasm that
tends to recur following excision. Proper management of these lesions is controversial and
includes various combinations of systemic therapy, radiation therapy (RT), and surgery.
Observation is now being advocated as a possible management option for select patients.
However, a readily available method for risk stratification is not available. Prior attempts at
deriving prognostic imaging biomarkers have not been successful, possibly due to small
numbers of patients.
Questions/Purposes: To determine if imaging features on pre-therapy MRI can be used to
predict progression-free survival in patients with extra-abdominal desmoid fibromatosis.
Methods: Waivers of informed consent and authorization to use and disclose protected health
information were granted from the IRB for this retrospective study. From 382 cases of desmoid
fibromatosis identified from our institution's tumor registry from 2000-2013, 90 patients met
inclusion criteria (extra-abdominal location, pre-therapy MRI, and at least 6 months of followup). The primary endpoint was progression (local recurrence of resected lesions or enlargement
of lesions treated with radiation or systemic therapy). Demographic and pathological data
(diagnosis, β-catenin mutation status) and treatment history (type and start and end dates of
treatment, surgical margins, type of surgeon, etc.) were obtained from the electronic medical
record. Initial MRI was assessed for location (e.g., neck, forearm, body wall, etc.), compartment
of origin (subcutaneous, superficial fascial, deep fascial, or intramuscular), extra-compartmental
spread (e.g., intramuscular lesion infiltrating into subcutaneous tissues), depth, multifocality,
shape, margin, extent of infiltrative margins, and degree and extent of T2 hyperintensity and
enhancement. Univariate and multivariable Cox proportional hazards regression models were
used to assess the relationship between these variables and time to progression. Kaplan-Meier
plots were used to estimate progression-free survival (PFS). Fisher's exact tests were used to
analyze the association between imaging features and mutation status (wild-type vs. other). All
statistical analyses were performed using SAS 9.3 for Windows.
Results: Patients were managed with observation (2.2%), surgery
(54.4%), radiation (8.9%), conventional chemotherapy (7.8%),
hormonal therapy (1.1%), tyrosine kinase inhibitors (TKI, 2.2%),
combination hormonal and TKI (2.2%), surgery followed by
conventional chemotherapy (2.2%), conventional chemotherapy and
RT (1.1%), surgery and RT (5.6%), and other combinations of
therapy (12.2%). Forty-four of the 90 patients had progressive
disease during the observation period (median: 3 year, range 0.58.9 years). Univariate analysis showed improved PFS for patients
with intramuscular (IM) or subcutaneous (SubQ) lesions (HR: 0.23,
95% CI 0.10-0.54). Multivariate analysis showed improved PFS for
Disclosure information may be found on pages 51-60.
patients with IM or SubQ lesions (HR: 0.22, 95% CI: 0.1-0.5), without added value from lesion
depth, shape, or location in body. This association held when surgical margins were considered
in the 47 patients who had resection. There was a significant improvement (p<0.001) in PFS
between patients with IM or SubQ lesions compared to those with superficial fascial or deep
fascial lesions (Figure). The median time to progression for patients with fascial lesions was 1.6
years (95% CI: 1.09-2.86), but could not be estimated for patients with IM or SubQ lesions, as
their PFS curves never fell below 50%.
Conclusions: Pre-therapy MRI can be used to detect patients at decreased risk for progression
regardless of therapy. Prospective studies will be needed to assess if these findings can be
applied to select patients for observation vs. therapy or in determining optimal observation
intervals.
Disclosure information may be found on pages 51-60.
SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 29
NON-RADIOGRAPHIC RISK FACTORS DIFFERENTIATING ATYPICAL LIPOMATOUS TUMORS
AND LIPOMAS
Authors: Lee Jae Morse1, Justin E. Bird1, Wei-Lien Wang2, Patrick P. Lin1, Bryan S. Moon1,
Alexander Lazar2,3, Robert L. Satcher1, John E. Madewell4, Valerae O. Lewis1,3
Institutions: 1Department of Orthopaedic Oncology, MD Anderson Cancer Center, Houston, TX,
United States.2Department of Pathology and 3Sarcoma Research Center, MD Anderson Cancer
Center, Houston, TX, United States.4Department of Diagnostic Radiology, MD Anderson Cancer
Center, Houston, TX, United States.
Background: Lipomas and atypical lipomatous tumors (ALTs) are the most common soft tissue
tumors found in the extremities. ALTs almost never metastasize but can be locally aggressive
and can potentially dedifferentiate, thus discerning ALTs from lipomas can be clinically relevant.
Some radiographic features help distinguish ALTs from lipomas but diagnostic uncertainty
arises when a large deep-seated lipomatous tumor does not display these characteristics.
Purpose: Determine non-radiographic risk factors differentiating lipomas from ALTs.
Methods: An IRB approved, retrospective chart review was performed on all patients with deepseated lipomatous tumors of the extremities treated from January 1, 2000 to October 1, 2010
at one institution. Patients were excluded if they did not have a final pathologic diagnosis of
lipoma or ALT, or underwent previous excision at an outside facility. Factors reviewed included:
age, gender, tumor location, size of lesion (greatest single dimension), biopsy and final
histologic diagnosis, and history of local recurrence, dedifferentiation or metastasis. Two
musculoskeletal pathologists performed a blinded, independent, randomized review of the
histologic slides to obtain diagnoses for comparison to the original, un-blinded diagnoses.
Fisher’s exact test or Chi-square test was used to evaluate comparisons of age and tumor
location in association with the diagnosis of lipoma or ALT. Wilcoxon rank sum test was used
to determine differences in age and tumor size between patients with a lipoma or ALT.
Multivariate logistic regression models were used to evaluate the effects of patient
characteristics (age >60y, gender, size >10cm, or thigh location) on ALT status. P-values less
than 0.05 were considered statistically significant.
Results: One hundred forty lipomatous tumors were included; 94 lipomas and 46 ALTs.
Patients diagnosed with an ALT tended to be older (mean 58.6 years) than patients diagnosed
with a lipoma (mean 53.3 years, p=0.017). The location of lipomas and ALTs differed
significantly (p<0.0001). Lipomas were evenly distributed between the upper and lower
extremities, 48.9% and 51.1%, respectively. Whereas ALTs predominately involved the lower
extremities (91.3%), 78.3% of which were located in the thigh. ALTs were significantly larger
(mean 20.9cm) than lipomas (mean 11cm, p<0.0001). The average length of follow-up for
lipomas was 35.4 months and 61.3 months for ALTs. Of the 140 tumors excised there was 1
(1.04%) recurrence in the lipoma group and 5 (10.9%) local recurrences in the ALT group.
Recurrence of the lipoma occurred 77 months after the index procedure in the ipsilateral arm
but the patient chose to not re-excise the lesion. The average time to recurrence for the 5
patients with ALTs was 39 months from excision (19 to 64 months). Two of these patients
chose to observe only, one patient had 2 subsequent recurrences, one patient underwent reexcision and is without recurrence 10 months after the last surgery, and one patient died 60
months after the last surgery with no reported recurrence. No cases of de-differentiation,
metastasis, or tumor-related deaths occurred in either the lipoma or ALT groups. A multivariate
logistic regression model showed that patients who were older than 60-years of age (OR 2.67,
CI 1.14-6.2), had tumors greater than 10cm (OR 8.11, CI 2.20-29.92), or their tumors were
Disclosure information may be found on pages 51-60.
located in the thigh (OR 4.06, CI 1.62-10.18), were at increased risk of being diagnosed with an
ALT as opposed to a lipoma. Male sex trended towards increased risk of an ALT diagnosis but
was not significant, p=0.059.
Conclusion: Risk factors that suggest a diagnosis of ALT such as age greater than 60 years,
tumors larger than 10cm, tumors located in the thigh, and possibly male gender may be used
to risk stratify patients with lipomatous tumors that do not display characteristic radiographic
features or present with an indeterminate biopsy. Excision may be recommended if the preoperative radiographic diagnosis between a lipoma and an ALT is unclear but the patient
presents with the above risk factors. Whereas observation may be recommended if they are
younger than 60 years, have a lipomatus tumor less than 10cm and it is located in their upper
extremity or leg. These risk factors may also be used to guide length and intensity of followup.
Disclosure information may be found on pages 51-60.
SESSION IV: SOFT TISSUE TUMORS
Saturday, October 11, 2014 | 11:15 AM – 1:00 PM
PAPER 30
MEDICAL MALPRACTICE AND SARCOMA CARE – WHO IS AT RISK AND WHY DOES IT
OCCUR?
Nathan L. Mesko, MD, Jennifer L. Mesko, JD, Lauren M. Gaffney, JD, Jennifer Lynne Halpern, MD,
Herbert S. Schwartz, MD, Ginger E. Holt, MD
Investigation performed at Vanderbilt University Medical Center, Department of Orthopaedic
Surgery, Musculoskeletal Oncology Division, Nashville, TN
Introduction: Increased attention on healthcare costs continues to drive pressures to provide
more efficient, quality care. Delayed recognition and abbreviated educational attention to rare
diseases, such as sarcoma, not only taxes the medical system, but also often leads to legal
consequences stemming from perceived gross deficiencies in care. We sought to identify filed
medico-legal cases related to extremity sarcoma malpractice with a goal of recognizing those
factors most commonly instigating sarcoma litigation. We hypothesized that a majority of
cases would be filed secondary to incomplete excisions and the subsequent morbidity
associated with the alteration in the care pathway, with surgeons being the most commonly
sued physician type.
Methods: Over one-million legal cases available in a leading national public legal database
(LexisNexis®) were searched for malpractice verdicts and settlements involving extremity
sarcoma using key terms “sarcoma” and “medical malpractice.” The query spanned the years
1980 to 2012. We categorized verdict/settlement resolutions by state, year, award amount,
and the nature of the complaint/injury. Each was reviewed for specialty of physician defendant,
academic affiliation of defendant, plaintiff age, sarcoma type/location, incidence of
claims/payments over time, and resolution outcomes by state.
Results: Of the 216 extremity/torso sarcoma litigation cases identified, 57% of case
verdict/settlements favored the Plaintiff. More than twice as many claims were filed in the last
decade (2000-2009; n=123) as compared to the prior decade (1990-1999; n=58). Delay in
diagnosis (81%; mean $2,277,718; 56% plaintiff decision) and unnecessary amputation (11%;
mean $1,936,814, 75% plaintiff decision) accounted for the majority of complaints. The average
disclosed award amount was $2,302,483 (n=61; range $65,076 – $12,661,611), with 33% of
awarded amounts remaining confidential. The average jury verdict award amount (45% plaintiff
decision; $3,955,560) was 2.7 times higher than average award amounts awarded through
settlement ($1,442,560). The greatest numbers of claims were filed against primary care
specialties (34%, mean $1,518,319), orthopaedic surgeons (23%; mean $4,125,285), and
radiologists (12%; mean $1,384,366). Sixty-percent of cases were in regards to complaints
surrounding soft tissue sarcoma recognition or care. The states with the highest number of
claims were New York, Pennsylvania, Massachusetts and Florida. State tort reform measures
were not protective against case resolution outcome.
Conclusions: Reported medico-legal claims involving sarcoma care continue to rise. Average
awarded amounts for sarcoma malpractice are 10-times higher than mean indemnity payments
for other reported medical/surgical specialties. Primary care and non-oncologic trained
orthopaedic physician specialties are the most commonly named physician defendants, citing a
delay in diagnosis. Physical injury stemming from incorrect or delayed surgery appeared a less
common malpractice instigator. This suggests further education in the front line recognition
and management of sarcomas is needed.
ACCREDITATION
This activity has been planned and implemented in accordance with the Essential Areas and
Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the
joint sponsorship of the American Academy of Orthopaedic Surgeons (AAOS) and the
Musculoskeletal Tumor Society (MSTS). The AAOS is accredited by the ACCME to provide
continuing medical education for physicians.
CME CREDIT
The American Academy of Orthopaedic Surgeons designates this live activity for a maximum of
11.25 AMA PRA Category 1 Credits. Physicians should only claim the credit commensurate
with the extent of their participation in the activity.
DISCLAIMER
The material presented at the Annual Meeting has been made available by the MSTS for
educational purposes only. This material is not intended to represent the only, nor necessarily
the best, methods or procedures appropriate for the medical situations discussed, but rather is
intended to present an approach, view, statement or opinion of the faculty, which may be
helpful to others who face similar situations.
The Musculoskeletal Tumor Society disclaims any and all liability for injury or other damages
resulting to any individual attending a course and for all claims, which may arise out of the use
of the techniques, demonstrated there in by such individuals, whether these claims shall be
asserted by a physician or any other person.
DISCLOSURE
Each faculty member in the Annual Meeting has been asked to disclose if he or she has received
something of value from a commercial company or institution, which relates directly or
indirectly to the subject of their presentation. The AAOS has identified the options to disclose
as follows:
n
1
2
3
4
5
6
7
8
9
= Respondent answered ‘No’ to all items indicating no conflicts;
= Royalties;
= Speakers Bureau (Speakers Bureau or Honorarium);
= Consultancies;
= Other Financial or Material Support;
= Stock or Stock Options;
= Research Support (Research or Institutional);
= Departmental or Institutional Support (Research or Institutional);
= Financial Support from Publishers (Financial or Material);
= Department Research or Institutional Support from Publishers;
An indication of the participant’s disclosure appears after his or her name as well as the
commercial company or institution that provided the support.
The AAOS and the MSTS do not view the existence of these disclosed interests or commitments
as necessarily implying bias or decreasing the value of the author’s participation in the course.
2014 MSTS Annual Meeting Speaker Disclosures
Albert J Aboulafia, MD (Baltimore, MD) 1 (Amgen Co); 4 (Amgen Co); 7 (AAOS); 8
(American Journal of Orthopedics; Clinical Orthopaedics and Related Research; Journal of
Bone and Joint Surgery - American; Journal of the American Academy of Orthopaedic
Surgeons; Orthopedics); 9 (Musculoskeletal Tumor Society)
Megan Aanstoos-Ewan, MS (Fort Collins, CO) (n)
John Alexander Abraham, MD (Philadelphia, PA) 3B (Biomet)
ADESEGUN ABUDU, FRCS (Ortho) (United Kingdom) 8 (Saunders/Mosby-Elsevier)
Vignesh Alamanda, MD (Charlotte, NC) (n)
Nicholas Kendall Allen (n)
Behrang Amini, MD, PhD (Houston, TX) (n)
Megan E Anderson, MD (Boston, MA) 9 (Musculoskeletal Tumor Society Education
Committee New England Orthopaedic Society Massachusetts Representative)
Luis Alberto Aponte-Tinao, MD (Argentina) 3B (Stryker); 8 (Clinical Orthopaedics and
Related Research)
Raffi Stephen Avedian, MD (Redwood City, CA) (n)
Miguel Angel Ayerza, MD (Argentina) 8 (Clinical Orthopaedics and Related Research);
9 (Association of Bone and Joint Surgeons)
Tessa Balach, MD (Farmington, CT) (n)
Andre Mathias Baptista, MD (Brazil) (n)
Thomas Beckingsale (United Kingdom) (n)
Natalie Beeler (Columbus, OH) (n)
Orjan K Berlin, MD (Sweden) (n)
Todd Eric Bertrand, MD (Tampa, FL) (n)
Odion Binitie, MD (n)
Justin Bird, MD - Program Committee (Houston, TX) 2 (Brainlab; Synthes)
Rachelle Bitton, PhD (Stanford, CA) (n)
Rickard Branemark, MD (Sweden) 3A (Integrum); 4 (Integrum); 9 (Orthopaedic
Surgical Osseointegration Society)
Julia A Bridge, MD (Omaha, NE) 7 (AFIP); 8 (Cancer Cytopathology; Cancer Genetics;
Journal of Orthopaedic Science; Modern Pathology); 9 (International Society of Bone and
Soft Tissue Pathology)
Carlos Enrique Brown Jr, MS (n)
Joseph A Buckwalter, MD (Iowa City, IA) (n)
Kim Butts-Pauly, PhD (Stanford, CA) (n)
Chapmen Cadell (Houston, TX) (n)
Nathan Calderon, MSc (Watertown, MA) 3B (Musculoskeletal Imaging Solutions)
Emily E Carmody Soni, MD (Rochester, NY) (n)
Simon R Carter, MD (United Kingdom) 2 (Biomet); 3B (Biomet); 5 (Biomet)
Edward Y Cheng, MD (Minneapolis, MN) 1 (Innomed); 3B (BONESUPPORT AB); 6
(Musculoskeletal Transplant Foundation); 8 (Journal of Bone and Joint Surgery American); 9 (Musculoskeletal Tumor Society)
David Cheong, MD (n)
Felix Ho-Ming Cheung, MD (Huntington, WV) 9 (West Virginia Orthopaedic Society)
Alexander Christ, MD (n)
Paul William Clarkson, MD, FRACS 5 (Stryker)
Mark Clayer, MD (Adelaide, Australia) (n)
Anthony Paul Conley (Houston, TX) (n)
Alex Cruz (n)
Judd E Cummings, MD (Scottsdale, AZ) (n)
Timothy A Damron, MD - Program Committee 5 (Cempra, Inc; Wright Medical
Technology, Inc. Genentech, Inc. Orthovita, Inc.; Stryker Zetrox, Inc); 6 (Stryker); 7
(Lippincott, Williams, and Wilkins; Wolters Kluwer Health - eMedicine UpToDate); 8
(Journal of Surgical Oncology eMedicine; World Surgical Journal); 9 (Musculoskeletal
Tumor Society; American College of Surgeons; AAOS)
Michael Deavers, MD (Houston, TX) 3B (Leica Biosystems); 7 (Wolters Kluwer Health Lippincott Williams & Wilkins)
Thomas F DeLaney, MD (Boston, MA) 3B (Amgen Co); 7 (Wolters Kluwer Health Lippincott Williams & Wilkins UpToDate , Oakstone Medical Publishing); 8 (Journal of
Clinical Oncology; Journal of Surgical Oncology)
Sander Dijkstra, MD (Leiden, Netherlands) (n)
Norbert Dion, MD (n)
Yee-Cheen Doung, MD (Portland, OR) (n)
Kyle Duchman, MD (Iowa City, IA) (n)
Nicole Ehrhart, DVM, PhD (Fort Collins, CO) 2 (Allosource, Inc)
Vahid Entezari, MD (Cleveland, OH) (n)
Nathan Evaniew, MD (Canada) (n)
Nicola Fabbri, MD (New York, NY) (n)
German Luis Farfalli, MD (Argentina) (n)
Peter Ferguson, MD (Canada) (n)
Marco Ferrone, MD, FRCSC 2 (Synthes)
Yale Fillingham, MD (Chicago, IL) (n)
Patricia Fox, MSc (Houston, TX) (n)
Douglas C Fredericks (Coralville, IA) 3B (Olympus biotech america); 5 (Medtronic
Sofamor Danek, Biostructures Inc., Olympus Biotech America)
Lauren Gaffney, Esq (Nashville, TN) 9 (American Orthopaedic Association;
Musculoskeletal Tumor Society)
Mark C Gebhardt, MD (Boston, MA) 7 (Clinical Orthopaedics and Related Research; Up
to Date;); 8 (Clinical Orthopaedics and Related Research;); 9 (International Society of
Limb Salvage; Massachusetts Orthopaedic Association; New England Orthopaedic
Society;)
David Samuel Geller, MD (n)
Pejman Ghanouni, MD, PhD (Stanford, CA) 5 (InSightec)
Michelle A Ghert, MD, FRCSC 9 (Musculoskeletal Tumor Society; Orthopaedic Research
Society)
C Parker Gibbs Jr, MD - Program Committee (Gainesville, FL) 3B (Exactech, Inc); 8
(Journal of Bone and Joint Surgery - American; Orthopedics)
Steven Gitelis, MD (Chicago, IL) 1 (Wright Medical Technology, Inc.;); 3B (Stryker); 4
(Wright Medical Technology, Inc.;)
Garry Gold, MD (Stanford, CA) 3B (Zimmer; Arthrocare; IsoTis Orthobiologics); 5 (GE
Healthcare); 8 (JMRI; Osteoarthritis and Cartilage); 9 (ISMRM)
Steven R Goldring, MD (New York, NY) 3B (Abbott (Wife); Bone Therapeutics, Fidia,
Janssen); 5 (Merck Serono (wife); Boehringer Ingelheim; Abbott (wife)); 8 (Arthritis
Rheumatism (wife) Osteroarthritis & Cartilage (wife)); 9 (Orthopaedic Research Society
(wife) Osteoarthritis Research Society International (wife))
Howard J Goodman, MD (n)
Mark A Goodman, MD (Pittsburgh, PA) (n)
Richard Gorlick, MD (Bronx, NY) 3B (Oncolytics, Inc); 4 (Oncolytics, Inc); 9 (Children's
Oncology Group; Connective Tissue Oncology Society; Foster Foundation; Sarcoma
Alliance for Research through Collaboration; Sarcoma Foundation of America)
Yair Gortzak, MD, MSc (n)
William Grant, EdD (Syracuse, NY) (n)
Robert John Grimer, FRCS (United Kingdom) 5 (Amgen Co); 8 (Sarcoma)
Ashleigh Guadagnolo, MD, MPH (Houston, TX) (n)
Jennifer Lynne Halpern, MD (Nashville, TN) (n)
Meera Hameed (New York, NY) (n)
John Robert Harris, MD (Little Rock, AR) (n)
Bryan Haughom, MD (Chicago, IL) (n)
Courtney B Haviland, BS (n)
John H Healey, MD, FACS (New York, NY) 7 (Clinical Orthopaedics and Related
Research;); 8 (Clinical Orthopaedics and Related Research; Journal of Orthopaedic
Science); 9 (Association of Bone and Joint Surgeons; Musculoskeletal Tumor Society;
Orthopaedic Research Society; Orthopaedic Research and Education Foundation;
Musculoskeletal Transplant Foundation ; AAOS)
Tyler Herzog, BS (Boston, MA) (n)
Kathryn Hess (Boston, MA) (n)
Werner Hettwer, MD (Denmark) (n)
John Hipp, PhD (Manvel, TX) 3A (Medical Metrics, Inc); 3B (Through Medical Metrics,
provide consulting for many different companies on imaging protocols and data
analysis); 4 (Medical Metrics, Inc)
Brian Paul Hobbs, PhD (Houston, TX) (n)
Ginger E Holt, MD - Program Committee (Nashville, TN) 9 (American Orthopaedic
Association; Musculoskeletal Tumor Society)
Francis J Hornicek, MD (Boston, MA) 3B (Stryker); 5 (Stryker); 6 (Biomet); 7
(Amyrsis; UpToDate); 8 (Journal Surgical Oncology); 9 (American Association of Tissue
Banks; FDA; ISOLS)
Chloe Horowitz (New York, NY) (n)
Matthew Houdek, MD (n)
Dali Huang (Omaha, NE) (n)
Ishaq Ibrahim, BS (n)
Marc Isler (Canada) 5 (Stryker); 8 (COA bulletin)
Stein Jasper Janssen, MD (n)
Jonathan K Jennings, MD (Birmingham, AL) (n)
Lee Jeys, FRCS 2 (Biomet); 3B (Biomet); 5 (Biomet)
Zhanhua Jia (Omaha, NE) (n)
Jennifer Wolff Jones, CAE - MSTS Staff (Rosemont, IL) (n)
Paul Jutte (Netherlands) (n)
Firouzeh Kamali, MD (Houston, TX) (n)
Cynthia M Kelly, MD - Program Committee (n)
Shah Alam Khan, MD (India) (n)
Joost Kortlever, BS (n)
Mark Krailo (Monrovia, CA) (n)
Harshad Ladha, MBBS, MPH (n)
Minna Laitenen (Tampere, Finland) (n)
Alexander Lazar, MD, PhD (Bellaire, TX) 2 (Norvartis; Merck; GlaxoSmithKline; Pfizer;
Astra Zeneca); 3A (GE Healthcare); 4 (GE Healthcare; 3M Healthcare; Johnson &
Johnson; Medco; Teva Pharmaceuticals; Zimmer Holdings Inc); 7 (Saunders/MosbyElsevier); 8 (Journal of Cutaneous Pathology (Wiley-Blackwell); Laboratory Investigation
(Nature))
Daniel M Lerman, MD (n)
Stephen Lessnick, MD, PhD 4 (Salarius Pharmaceuticals); 7 (UpToDate); 8 (American
Journal of Translational Research; Frontiers in Cancer Genetics; Frontiers in Pediatric
Oncology; Sarcoma); 9 (Connective Tissue Oncology Society)
G Douglas Letson, MD (Tampa, FL) 3B (Stryker); 9 (Florida Orthopaedic Society)
Valerae O Lewis, MD - Program Chair (Houston, TX) 5 (Stryker); 8 (Hindawi Publishing
Corporation; Orthopedics Today); 9 (AAOS; AAOS; Western Orthopaedic Association)
Patrick P Lin, MD - Program Committee (Houston, TX) 4 (Gilead Sciences); 5 (Pfizer);
7 (Springer); 9 (Musculoskeletal Transplant Foundation)
Xiao-Qiong Liu, PhD (Omaha, NE) (n)
Megan Lusk - MSTS Staff (Rosemont, IL) (n)
Charles Lynch, MD, PhD (Iowa City, IA) 5 (Eli Lilly Novo Nordisk)
John Edward Madewell, MD (Houston, TX) (n)
Isabella Mak, BS, MSc (n)
Allison Malandra, DVM (Coralville, IA) (n)
Kenneth A Mann (Jamesville, NY) (n)
Neyssa Marina, MD, MS (Palo Alto, CA) (n)
Richard Louis McGough, MD - Program Committee (Pittsburgh, PA) 3B (Stryker); 5
(DePuy, A Johnson & Johnson Company); 9 (Musculoskeletal Tumor Society)
Elizabeth McIlvaine (Monrovia, CA) (n)
Nathan Wesley Mesko, MD (n)
Jennifer Mesko, JD (Cleveland, OH) (n)
Benjamin J Miller, MD (Iowa City, IA) (n)
Laura Monovich (Columbus, OH) (n)
Corey O Montgomery, MD (Little Rock, AR) (n)
Michael Monument, MD (Canada) (n)
Bryan Scott Moon, MD (Houston, TX) (n)
David C Moore (Nashville, TN) (n)
Jose A Morcuende, MD (Iowa City, IA) 9 (AAOS USBJI POSNA)
Shawn Morrell, MD (Little Rock, AR) (n)
Carol D Morris, MD, MS - Program Committee (Baltimore, MD) 9 (AAOS)
Lee Morse, MD (n)
Domingo Luis Muscolo, MD (Argentina) 8 (Clinical Orthopaedics and Related Research;
Orthopedics)
Ara Nazarian (n)
Richard W Nicholas Jr, MD (Little Rock, AR) 6 (Musculoskeletal Transplant Foundation)
Lukas M Nystrom, MD (Maywood, IL) (n)
Megan E Oest, PhD (Syracuse, NY) (n)
Polina Osler, MBBS (Boston, MA) (n)
Jesse E Otero, MD (Iowa City, IA) (n)
Rishabh Dev Phukan, BA (Boston, MA) (n)
Snezana Popovic (Canada) (n)
Shannon Puloski, MD, FRCSC (Canada) (n)
Ed Purdue, PhD (New York City, NY) (n)
Ajay Puri, MD (India) 8 (Bone and Joint 360; Sarcoma)
Robert H Quinn, MD (San Antonio, TX) 5 (Musculoskeletal Transplant Foundation); 9
(AAOS; American Orthopaedic Association; Musculoskeletal Tumor Society; Wilderness
Medical Society)
R Lor Randall, MD (Salt Lake City, UT) 2 (Biomet; Biomet); 5 (Musculoskeletal
Transplant Foundation); 8 (Annals of Surgical Oncology; Clinical Orthopaedics and
Related Research; Journal of Surgical Oncology; Peer Case; World Journal of
Orthopaedics); 9 (AAOS; American Orthopaedic Association; American Society of Clinical
OncologyASCO; Association of Bone and Joint Surgeons; Children's Oncology Group;
Children's Oncology Group (COG); Connective Tissue Oncology Society; Musculoskeletal
Transplant Foundation; Musculoskeletal Transplant Foundation; Musculoskeletal Tumor
Society; National Cancer Institute; National Cancer Institute, National Institute of
Health; National Comprehensive Cancer Network; National Comprehensive Cancer
Network; Sarcoma Foundation of America; The MHE Research Foundation)
Kevin A Raskin, MD (Boston, MA) (n)
Deena Rawlings - MSTS Staff (Rosemont, IL) (n)
John E Ready, MD (Boston, MA) 3B (Smith & Nephew)
Krishna I A Reddy, MBBS, MS, FRCS (Ortho) (n)
Dan Regan, DVM (Fort Collins, CO) (n)
Nickolas Bernard Reimer, MD (n)
Ruth Rose, DVM (Fort Collins, CO) (n)
Robert L Satcher Jr, MD (Houston, TX) 9 (AAOS)
Thomas J Scharschmidt, MD (n)
Joseph Hasbrouck Schwab, MD 2 (Synthes Stryker Spine); 3B (biom'up); 6 (Globus
Medical stryker); 9 (Biom'up)
Herbert S Schwartz, MD (Nashville, TN) 6 (Musculoskeletal Transplant Foundation); 9
(American Board of Orthopaedic Surgery, Inc.)
Marcos Galli Serra, MD (Argentina) 9 (Asociacion Argentina de Ortopedia Oncologica;
Comite de investigacion Asociacion Argentina de Ortopia y Traumatologia)
Herrick Siegel, MD (Birmingham, AL) 2 (Biomet; Corin U.S.A.; Stanmore; Stryker); 3B
(Biomet; Corin); 7 (American Registry of Pathology); 8 (Journal of Foot and Ankle
Surgery; Orthopedics Today); 9 (Musculoskeletal Tumor Society)
Franklin H Sim, MD (Rochester, MN) 7 (Saunders/Mosby-Elsevier)
Brian Snyder, MD, PhD (Boston, MA) 9 (Pediatric Orthopaedic Society of North
America; Scoliosis Research Society)
Yanna Song, MS (Nashville, TN) (n)
Jeff W Stevens (Iowa City, IA) (n)
Richard M Terek, MD (Providence, RI) 4 (Norvartis; Pfizer; Astrazeneca; Johnson &
Johnson); 7 (Lippincott); 8 (Clinical Orthopaedics and Related Research); 9
(Musculoskeletal Tumor Society, Rhode Island Orthopaedic Society, New England
Orthopaedic Society)
Roger Tillman, FRCS (United Kingdom) (n)
Mohammad Toliyat (Houston, TX) (n)
Richard Tozer (Canada) (n)
Robert Emile Turcotte, MD FRCSC (Canada) 9 (Canadian Orthopaedic Association;
Musculoskeletal Tumor Society, Quebec orthopaedic Association. International society of
limb salvage)
Hazem Wafa, MD (United Kingdom) (n)
Eric R Wagner, MD (Rochester, MN) (n)
Matthew T Wallace, MD (Washington, DC) (n)
David Wang, MS (Bronx, NY) (n)
Wei-Lien Wang, MD, MPH (Houston, TX) (n)
Kristy L Weber, MD - Program Committee (Philadelphia, PA) 7 (Wolters Kluwer Health Lippincott Williams & Wilkins); 8 (Current Surgery Reviews; Journal of Bone and Joint
Surgery - American); 9 (Musculoskeletal Tumor Society; Orthopaedic Research Society;
Ruth Jackson Orthopaedic Society)
Kurt Richard Weiss, MD (Pittsburgh, PA) 3C (I am on the scientific advisory board of
Eleison pharmaceuticals. I have received exactly $0.00 thus far from this position.)
Joel Michael Werier, MD (Canada) (n)
Benjamin Wilke, MD (Rochester, MN)
Richard B Womer, MD (Philadelphia, PA) (n)
Cody Wyles, BS (n)
Joel P Zarling, MD (Houston, TX) (n)
David Zurakowski PhD (Boston, MA) (n)
MUSCULOSKELETAL TUMOR SOCIETY
Vision: The Musculoskeletal Tumor Society will be a
recognized authority on all aspects of orthopaedic
oncology, an influential participant in policy-making for
orthopaedic oncology services, and responsive to the needs
of orthopaedic oncologists and their patients.
Mission: The Musculoskeletal Tumor Society will advance
the science of orthopaedic oncology and promote high
standards of patient care through excellence in education
and research.
Objectives
Membership: Serve and engage current and prospective
orthopaedic oncologists
Education: Serve as the premier provider of education in
musculoskeletal oncology
Research: Encourage and support meaningful, relevant,
and timely research for the advancement of knowledge in
musculoskeletal oncology
Organizational Excellence: Become and maintain a
healthy and viable Society